posterpresentationsjnm.snmjournals.org/content/22/6/p61.full.pdf · 2006-12-25 · first anrothed...

I'ROULLDINGS 01: TIlE 28th ANNUAl. MEETING

CardiologySection,Departmentof Medicine,UniversityofOklahoma,Oklahoma City, Ok.

Thepurposeof thisstudywas to developa methodforquantifyingregional left ventricular(LV) functionusingmultiple gated equilibriumscintigraphyand to test thevalue of the method to predict specificcoronary artery(CA) disease as determinedby contrastangiography.Seventeenpatients (PTS),who underwentcontrastangiography,were imaged in the left anterior oblique view atrest and during supine ergometerexercise. The LV regionsof interest CR01)were determinedusing a second derivativeedgedetectionalgorithm.Eightsectorsof 45Â°eachwere constructedabout the geometriccenter of the enddiastolicROI. From the backgroundcorrectedcounts ineachsectora regionaltimeactivitycurvewas generated.A regionalejection fraction (REF)was calculatedas thepercent change from the maximum to the minimum value ofeach curve. In the PTS studiedwith hemodynamicallysignificant (>70% narrowing)lesions,6 were found in theleft anterior destending,5 in circumflexand 5 in theright CA. Any increase in exercise REF was considerednormal. The sensitivity(SN), specificity(SP) andaccuracy (A) of identifyingdiseased CA by this methodwas 88, 78, and 82%, respectively. The global ejectionfractionresponse to exercise provideda SN of 83%, SPof 53%, and an A of 54%. These results indicatethatREF analysis provides greater accuracy without loss ofsensitivitywhen compared to global ejection fractionanalysis.

CLINICAL.USEFULNESSOF EMISSION CT BY A ROTATING GAMMACAMERA. T.Mukai,Y.Ishii,K.Yamanioto,N.Tamaki,H.Maeda,H.Ito,K.Minato,R.Morita,Kâ€¢Torizuka.Kyoto UniversityHospital,Kyoto,JAPAN.

Our single photon emission CT(SPECT)using a rotatinggamma camera (400-T;GE)and computer(PDP1l/60;DEC)withadditionalsoftwaresand devices was evaluatedclinically.Convolutionmethod using a high cut filter and attenuationcorrectionusingmodifiedSorenson'smethodwereadoptedforreconstructionalgorism.Processingtimetook20 sec/slice for 64 view data. Phantom studies using 20 x 30 cmellipse phantom with Tc-99m revealed sensitivityof 1.4kcps/uCi/ml.Resolutioncapabilityof 1.5 cm FWHM,eitherathorizontalor verticaldirection,unrelatedto depth wasachieved.For clinicaluse,it took about 10 mm. for vanousTc-99mstudies,2Omm. forTl-201myocardialstudyandmore than 40 mm. for ECG gated heart studies,inwhich theformer two studies seemed to be permissiblefor routinecheck-up,providinghigher clinicalefficacy than by conventionalplaner images.However,theECG gated study shouldbe limitedfor a selectedcases suspectedto have a subtlewall motion abnormality.Asoftwarefor multiple choice oftomographicsectioningsuch as transaxial,frontaland sagittal was made to help detectingsmalle SOLs in a bulkyorgan such as in liver and locatingischemlcdefect of myocardium in tangentialplane, For perfusion lung study,aflood source was added to attach opposing to camara face,allowingto obtain transmissionCT simultaneously,inthesame geometricalslice,thusto locate a marginal perfusiondefect easily and to define perfusionvolume value quantitatively. In conclusion,SPECTwith additionalmodificationhas became superioralternativefor conventionalscintigraphy in our labolatory.

TWO METHODS OF NONSTATIONARYIMAGE PROCESSINGUSING THESIGNAL-TOâ€”NOISERATIO AS THE CRITERION IN FILTER DESIGN.M.A. King, P.W. Doherty. The Universityof MassachusettsMedical School, Worcester,MA.

In stationaryimage processingno account is taken ofregional signalâ€”toâ€”noiseratios (SNR) in deriving theprocessedimage from the unprocessedimage. Nonstationary techniques,however,allow filteringof the image forprimarilynoise suppressionin low SNR regions and resolution recoveryin high SNR regions. Two methods of nonstationary image processingwere investigatedin this studyusing frequencyspace filters in which the cutoff forresolutionrecoveryand the amount of smoothing @redependent on local SNR.

The first method consistedof breaking the image upinto a square array of redundant (overlaping) segments

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Volume 22,Number 6 P61

THURSDAY, JUNE 18, 1981

POSTER PRESENTATIONS

ROOMS L and M

COMPUTER AND DATA PROCESSING

LEFT VENTRICULAR EJECTION FRACTION: THE FIXED VERSUS THEVARIABLE REGIONâ€”OF-INTEREST (ROl) METHODC.W.J. Schiepers, C.N. de Graaf and P.P. van RijkInstitute of Nuclear Medicine, Utrecht, The Netherlands

The effect on EF of various methods and background (BC)correction was investigated. In the FIXEDâ€”ROImethods (FIX)only I LVâ€”ROIis used both for endâ€”diastole(ED)and endsystole(ES). In the VARIABLEâ€”ROImethods (VAR) more LVâ€”ROIsare used for a heart cycle, i.e. I for ED and I for ES. InFIXI the ROI was drawn directly on the ED display and inFIX2 both a phaseâ€”amplitudeimage and the ED display wereused. The VARâ€”methodsonly differed with respect to BGâ€”correction: VARI used 2 BGâ€”ROIs,VAR2 only I and VAR3 a cycleaverage just as in the FIXâ€”methods.

There were 25 heart studies and 4 observers; each EF wasdetermined once. The range of EF's was .05â€”.76 Comparisonof observer averages showed EF of the VAR-methods alwayshigher than those of FIX by about .10 The interâ€”observervariability of FIX1 and VAR3 were about the sane,the othersgreater; average s.d. per heart study was about .04

Theoretically, the relation between EF's determined fromraw and BC corrected LVâ€”volumecurves has to be linear;thissituation was fairly well accomplished in our limited data(correlation .85). On average the BC level was 55% of rawLV counts and increased a little from outward to inward.Assuming a constant BC level, BC correction in the FIXethods only affects the denominator in EF, the numeratorcancels out. In the VAR-methods both denominator and numerator are influenced, because of more ROIs. Thus, the FIXmethods are more sensitive to drawing errors and the VARmethods appear none appropriate. BC correction by an average level over the heart cycle minimizes influences due tostatistical fluctuations, making VAR3 the preferable methodas witnessed by low interâ€”observervariability.

CALCULATIONOF TRANSVERSE-VENTRICULARSECTIONS FROM TRANSAXIAL ECT RECONSTRUCTIONSOF THE MYOCARDIUM. D.0. Olson,D.L. Williams,J.L. Ritchie,G.D. Harp, and G.W. Hamilton,VA Medical Center and Universityof WashingtonSchool ofMedicine,Seattle,WA; and G. Gullberg,R. Eisner,andD. Nowak, General ElectricCompany,Milwaukee,WI.

The effectivenessof emission computedtomographyas aclinicaltool depends on the optimizationof the observation directionfor the organ of interest.

For many tracer studies (i.e., sulfur colloid liverscans), standardtransaxialtomogramsmay well be adequate.Others (particularlycardiac)can be enhanced by takingadvantageof basic organ symmetry.

Beginningwith thalliummyocardialtransversesectionsreconstructedfrom a G.E. 400T tomograph,we have developed a means of re-orientingthe major cardiac axis tooptimallyobserve left and right ventricularperfusionwith minimal data degradation. Transverseaxial tomogramshave been reconstructedfrom 128 x 128 projectionimagesin serial slices two projectionbins apart (6 mm planespacing)and were displayedon a 64 x 64 grid. Reorientationof the transaxialmyocardialimages in an apexto-base presentationis achieved by four Image manipulations which includetwo coordinaterotationsand two sorting operations. The computer program has been tested onthe Iowa heart phantom and clinical images. No significant data alterationhas been observed.

REGIONAL LEFT VENTRICULARTIME ACTIVITY CURVES FROM MULTIPLE GATED EQUILIBRIUMSCINTIGRAPHY:CORRELATIONWITH CONTRAST ANGIOGRAPHY. R.D. Burow, M.F. Wilson, E.W. Allen,and E. Schechter. VA Medical Center ResearchService and

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I'ROCI@IDINGs 01 TIll 28th ANNUAl. MI@I@rIN;

centered on pixels every fourth row and coltmin. Eacnsegment was two-dimensionallyFourier transformed,f11-tered, inverse transformed,and multipliedby a bilinearInterpolatingfunctionwhich determinedthe fractionofthe pixel count to be used in forming the final image.The secondmethod is computatlonallymore efficient,butlessregionallyspecific.A highlysmoothedimageandonefiltered according to the maximumSNRpresent in the Imageare produced. The final image is constructed as theweighted sun of these two Imageswith the weIght being thefractionof the maximtsnSNR for each pixel. The timetaken to process Images using these techniqueshas beendecreasedfromminutesto secondsby theadditionof anarrayprocessor(analogicAP400)to oursystem.

These processing techniques have shown significantimprovement in image quality when evaluated with testphantomsand clinical images.

EVALUATIONOF MEDIAN FILTERINGON SCINTIGRAPHICIMAGES.COMPARISONWITH LINEAR AND [email protected]. Deconinck,R. Lepoudre.AZ-VUB, 1090 Brussels,Belgium.

In this study we have evaluatedthe use of median filteringas an alternativeto conventionallinearor non-linearsmoothing. The different filterswere developpedon a minicomputer for nuclearmedicine (InformatekSimis 3). In linearconvolutionsmoothingeach pixel is replacedby a weightedaverage of its original value and its neighbours.Convolution smoothing is equivalentto multiplyingthe frequencydistributionof the image in Fourier space by a fixed frequency filter which blurrs rapidly varying structuresinthe image such as noise and edges. In median filteringeachpixel is replacedby the median of its original value andits neighbours.Median filteringdoes not correspondto afixed frequency filter. Individual pixel noise is suppressedbutedgesarenotblurred.Multiplemedianfilteringonan image rapidly converges to quasi stable images.We haveevaluated five median filters,three linear and one non-linear smoothingtechnique : simultaneous5 pt diagonalcross,sequential3 pt first and second diagonal,simultaneous5pt verticaland horizontalcross, sequential3 pt horizontal and vertical line, 9 pt square median filter ; 9,25,81pt convolutionsmoothing ; non-linearvariableshape smoothing. The differentfilterswere evaluated for loss ofclinical information,suppressionor generationof artefacts and imagesharpness.The sequentialhorizontal-vertical as well as the 9 pt square median filters are preferredto conventionalsmoothingtechniquesfor the rejectionofaberrant image points or lines without blurringthe image.Median filteringis thereforeparticularlyattractiveforfilteringhigh resolutionimages (e.g. seven-pinholeacqulsition in 128 x 128 format) or when subsequentedge detection is required (e.g. nuclear angiography).

A @1PARIS@ OF FUNCTIc@AL IMAGI@ METHcIJS. C.R. Appledorm , B . E. ck@penheim, and G.N. Saridis. Indiana UniversitySclwol of Medicine, Indianapolisand Purdue University,West Lafayette, IN.

A functional (or parametric) image is generated by cobbecting a sequence of inmges at discrete intervals of timeforming the tine-activity curve for each pixel sequence,evaluating acme parameter describing the curve shape, anddisplaying the parameter values as a digital inmge. Theproblem we examine bere is the method with which parametervalues are actually evaluated in high noise situations.

We have described previously several parameters that areapplicable to the functional inmging of the dynamic renalstudy and the identification of renovascular disease. ()ieparameter, ThIAX,describes the time-to-peak of the pixelcurve. Its value is influenced greatly by curve noise,hence the evaluation method meat car@ensate for curve noisecontent.

Four methods for parameter value evaluation are canpared: 1) Direct, in which the original curve is directlyoperated upon , 2) @ixoth , in which the original curve isfirst anrothed , 3) Factor , in which factor analysis is applied â€¢and 4) Mininun Variance , in which a variation of thefactor method is employed. The mininun variance method isborrc@d fran the field of estin@tion theory and has notbeen used previously for this application.

In carputer simelation studies and in a series of patient studies, this curve shape parameter describing dy

manic renal stuthes were evaluated. The direct and @sroothmethods were shown to provide very poor estiii@tion schemes.The factor method and the mininun variance method consistently outperfonn tbern. The mininun variance metlxd issupeiâ€¢ior to the factor method in high noise situations.

TOMOGRAPHICBLURCOMPENSATIONALGORITHMSFORTHE PHO/COM192 SCANNER. E. Garcia, J. Areeda, D. Chapman,S. Rudin,J. Diaz, D. Berman, A. Waxman. Cedars-SinaiMed Ctr, LA, CA

Previous blur compensationalgorithms for limited angletomographyhave been limited by noise propagationor by notbeing compatiblewith the acquisitionand projectioncharacteristicsof the Pho/Con (PC). Thus we developedan analytic (An) algorithm (A) in the form of a filteringfunctionwith a filter appropriate to the 3 dimensIonal reconstruction geometryaid an Iterative (ItA) similar to unsharpmasking. With AnA, each scintillationevent Is filteredasit is read, and the result is back projected,with the debldrred image being created as events accumulate. The ItAassumesthatbackprojectedcountsabovea thresholdsignify activity onginating at that plane. Fromthe locationand magnitudeof these counts, the blurringpattern is generated in the form of tip-to-tip cones, which are partiallysubtracted from the neighboring planes. ItA Is ten timesfasterin executionthanAnA. BothapproachesresultedinincreasedImage contrastina variety of phantomand patientstudies using previousgenerationcomputer (MDS modumed)and Imaging (PC-072)systems. To circumventlimitationsinlong reconstruction times and detector efficiency, we haveinterfacedthe PC-192 to the MDS A2 system. The PC-192offers improved detectors with more photomultipliers (19),larger diametercrystals (9.3'),thinner crystals (@â€˜)andImprovedelectronics. The A2 offers largermain (128Kwords)andremote(256Kwords)memories,a larger(80megabytes)and fasterstoragediskandan improvedvideodisplay with 252 gray levels. With this advanced Instrumentation, implementation of these algorithms, particularly thefaster unsharp masking, results In short reconstructiontimes of contrast-enhancedimages, therebymaking clinicallyapplicablethis approach to longitudinaltomography.

GFIT: A COMPUTER PROGRAM FOR QUANTITATION OF LEFTTORIGHT CARDIAC SHUNTS . G .R . Cardell and D .D . Patton.University of Arizona Health Sciences Center, Tucson, AZ.

A program written for a Digital Equipment Corporatics'

computer (PDP 11/34) is described which enables the userto fit a gamma-variate function to lung time-activitycurves after a bolus injection of Tc-99m. The program,written in Fortran IV, makesuse of an iterative steppingroutine to explore the parameter space, choosing the pointwith the lowest sum of least squares. Requiring no usersupplied initial estimates, the method is simple and hasan advantage over analytical methods which are very sensitire to proper selection arrival of time, point of maximumconcentration, and point of recinculation.

Running time of the program is about 2 nina . and itsrelatively small size (12K) allows it to nun in the background mode of an RT-ll operating system. Several statistics (correlation, coefficient, chi-square test, Fâ€”test,and percent variability explained) are included toevaluate the adequacy of the fit and the accuracy ofestimated parameters.

Seven patients were studied with cardiac catheterizationand with the GFIT program. Close agreement in Qp/Qs ratios(r = 0.82, p < 0.025) suggests this method is sufficientlyreliable to be used as a screening test for the detectionand quantitation of left-to-right cardiac shunts.

The program' s advantages are greater freedom fromoperator subjectivity, rapidity, small size, and displayof raw and fitted curves, along with relevant statisticaldata.

THE DETERMINATIONOF FIRST PASS RIGHT HEART EJECTIONFRACTIONWITH A CONVENTIONALANGER CAMERA. R.T. Go, S.A.Cook, W.J. Maclntyre,T.S. Houser, J.M.K. Celmo, and 0.5.Moodie, ClevelandClinic Foundation,Cleveland,Ohio.

ConventionalAnger cameras have been infrequentlyusedin quantitativefirst pass studies of right heart ejectionfractionbecause of limitationsof their response to high

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study. This algorithm Is designed for on-line analysisofcardiac functionduring exercise protocol,pharmaceuticalInterventionsand routine clinicalcardiac studies. Theapplicationof this type of on-line analysis should bevery ussful In the reduction of risk during interventionstudies.

FINITE LENGTH FILTER KERNEL GENERATION FOR TOMOGRAPHY.N.H. Clinthorne, and W.L. Rogers. University of MichiganMedical Center, Ann Arbor, MI.

When ECT images are reconstructed in the spatial domainby convolutionâ€”backprojection,the length of the convolvingsequence corresponding to most filters is infinite. Thismeans that the convolution length must be twice the projection length. Reconstruction time can be significantly reduced by decreasing the convolution length, however, directtruncation often produces artifacts in the reconstructedtomograms.

To alleviate this problem, the Remez exchange algorithmhas been used to construct finite length sequences in thespatial domain to represent desired frequency responses.Given the sequence length, frequency response, and errorweighting function, the algorithm calculates the spatialdomain sequence of specified length which is optimal in thesense that the weighted Chebyshev error from the desiredfrequency response is minimized. Several reconstructionfilters realizable in less than oneâ€”fifthof the projectionlength have been designed which exhibit little loss in reconstructed image quality yet reduce reconstruction timeby 75Z.

Computing times for ECT image reconstruction in the spatial domain can be significantly reduced with minimal imagedegradation by using optimized finite length convolutionkernels calculated by the Remez exchange algorithm.

HOT-SPOT @1ISSION TOMOGRAPHY OF THE MYOCARDIUM: ASIMULATION STUDY OF ATTENUATION EFFECTS. M.Lewis,E.Stokely, L.Buja, J.Willerson, F.Bonte, S.Lewis, R.Parkey. U. Texas Hbth. Sci. Center at Dallas, TX

Bones, lung, and soft tissues present varyingphotonâ€”attenuationcharacteristics ; thus , singleâ€”photonemission tomography of the thorax may be inaccurateunless attenuation compensation is provided. With hotspot imaging agents such as technetiumâ€”99mstannouspyrophosphate (Tcâ€”PYP), however, detection and/orsizing of@lesions may not be compromised by attenuationeffects. A computerâ€”based simulation was done toassess the impact of attenuationon tomographicreconstruction of myocardial infarct ((41)labeled withTc-PYP. Thorax models were generated, includingrealistic attenuation and three MI:background activityratios. Projection data were obtained with varyingamounts of Poisson noise, varying numbers ofprojections, and either halfâ€”or fullâ€”circledata.Three reconstructions were done using the Filtered BackProjection (FBP) method: with no attenuationcompensation, and with simple exponential and geometriccorrection schemes; a fourth reconstruction was donewith the Iterative Relaxation method, using the trueattenuation profiles. The resulting images wereevaluated according to lesion sizes, and a sumof-squares error measure (SSE). The iterative methodgave better visualization of posterior structures suchas vertebrae,and it gave lowerSSE than the othermethods for 2:1 and k:i activity ratios. However, theuncorrected FBP method used the least computer time,gave the most accurate MI sizes, and gave thelowest SSE for the 8:1 activity ratios.

AUTOMATIC RECOGNITION OF FOCAL LIVER SCAN DEFECTS. S.L.Fritz, D.F.Preston, N.L.Martin, J.H.Callagher,R.G.Robinson.University of Kansas Medical Center, Kansas City, KS.

The purpose of the report is to describe a numericalapproach which identified metastatic cancer in digitizedTcâ€”sulfurcolboid liver scintigraphs. Of 125 patients haying liver scans, a total of 35 met criteria for proof ofnormality or abnormality at a specific location in the liven. The anterior view of each study, digitized in a 64x64array, was then analyzed numerically. The outline of theliver was obtained by gradient and threshobding techniques.

count rates. The present study has demonstratedthat provided a sufficientlyrapid injectioncan be accomplished,data suitable for accurate right heart ejection fractioncalculationscan be acquiredwith this instrument.Multiple frames of 0.05 sec. durationwere recordedon

32 x 32 matrices for 45 seconds followinginjection. Theright ventricleregion of interestwas selectedby anautomaticchest parser and a histogramrecord was plottedout. In most cases, the injectionwas sufficientlyrapidso thata stepfunctionof injectionwasobservedwiththree to four cycles usually availablefor analysis. Thehistogramwas filtered to reduce noise variationwithouttemporaldistortionof the curve. The ejection fractionwas calculatedfrom differencesin successiveenddiastolicand end-systoliclevels. Correctionfor contaminationfrom right atrium in the anterior portionwasbased on the estimateof 25% proposed by Bergen, et al@In a series of 21 children and adults with congenital

heart disease, correlationwith right heart contrastventriculographyshowed an â€œrâ€•value of 0.85.This determinationis now being performedon all pat

ients referred for radionuclideleft-to-rightheart shuntdeterminations.1. Berger, H.S., Matthay, R.A., Loke, J., Marshall,R.C.,Gottschalk,A., and Zaret, B.L., Am. J. Cardlol.41897-905, 1978.

ANALYSIS OF VENTRICULAR CONTRACTION ABNORMALITIES IN AMPLITUDE/PHASE SPACE - THE STROKE VOLUME VECTOR MAP . DW Shosa,JW O'Connell, ES Botvinick, MA Frais, RS Hattner, University of California, San Francisco, CA

Extraction of the dc component and first Fourier temporalharmonic from gated scintigraphic images of the cardiacblood pool result in an approximation to the count densityin a ventricular region (R) of the image.

The extraction produces three images: C0(x,y,) is the dccomponent image. C@(x,y) is the amplitude image. @(x,y)isthe phase image.Although conduction abnormalities (in the absence of cont

raction abnormalities) are easily elicited from the phaseimage, a complete analysis of contraction abnormalities requires integration of information from both â€¢(x,y)andcl(x,y). The stroke volume is the interesting parameterand it is a vector quantity. The amplitude is given by

ISvIR@ Cicos@)2 + (@ Clsine)}Â½

We suggest the use of an â€œimageâ€•in (C1,$) space whichhas intensities proportional to the number of pixels in Rwhich have amplitude C1 and phase $. The image is a â€œhistogramâ€•of the ventricle not dissimilar to a phase imagehistogram except that it has a twoâ€”dimensionalbase. Methode of extracting diagnostically significant statisticsfrom such images will be discussed.

AUTOMATEDON-LINE ANALYSISOF ALL FOUR CARDIAC CHAMBERSFOR RAPID SETUP, @TAACQUISITIONAND REDUCTION. T.R.Nelson,G.C.Perkins,R.A.Slutsky,J.W.Verba. VeteransAdministrationMedical Center and Universityof California,San Diego, CA.

An algorithmis presentedfor the automaticon-lineanalysis of all four chambersof the heart throughout thecardiaccycle. Thisalgorithmis Intendedto allowfaston-line evaluation of the patient Imaging angle for optimIzing the patient positionand establishingbaseline parameters. On-the-flyâ€œListModeâ€•breakup will adapt tochanging heart rate. Threeâ€”dimensionalspace and time filters are applied to the data frames to increasetheirstatisticalaccuracy. The temporaland spatial behaviorofeach pixel Is monitored throughout the cardiac cycle, andpoints meeting phase, amplitudeand derivativecriteriaare assigned to one of the four cardiac chambers. Background activity for each chamber Is calculatedseparatelyusing the camera's point spread response characteristics.Volume curves are generatedfrom dynamic regions for eachchamber, with both right and left ventricular ejectionfractionsand atrial contributionsto filling calculatedonâ€”line.Once Initial conditionshave been established,the algorithmwill monitor trends and parametersspecifiedby the physician. These will be updated rapidly to allowmonitoringto keep pace with changingconditionsof the

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I'ROCIEI)IN(;s OF TIlE 28th ANNUAl. MII:TIN(;

Within the liver boundary, candidate lesions, defined aslocalized regions of bow activity, were detected with aLaplacien function. Twelve numerical measures were devisedfor such diagnostic features as contrast and sharpness oflesion edges, extraâ€”hepaticuptake, etc. Actual lesions inpatients with abnormal scans were located by association ofcandidate lesions with known metastatic lesions where possible. All candidate lesions not so identified were labelled normal if found in a patient with a normal diagnosis,and unknown otherwise. Feature values of the known positive and negative candidate lesions were used to constructa Fisher's linear discniminant function, which was thenused to determine whether a metastatic lesion was found ineach patient image. Variation of the discniminant functionthreshold allowed construction of an ROC curve for numenical diagnosis. This curve was compared to a compositeROCcurve describing clinical diagnostic performance of 4417liver scintigrams reported in the literature. This companison showed that numerical diagnosis using only the anteriorview was less accurate than average reported clinical performance, but was within the range of performance demonstrated by human observers.

METHOD TO ESTIMATENOISE AND SIGNAL LEVELS IN NUCLEAR MEDICINE IMAGES AND AN ALGORITHM TO REDUCE THE NOISE. C.C.Kuni, B.H. Hasegawa,W.R. Hendee, J.P. Gerhold. Universityof Colorado Health Sciences Center and the Veterans AdministrationMedical Center, Denver, CO.

Commonly used methods of reducingstatisticalnoise innuclear medicine Images rely on lowpassfilteringwhich hasthe disadvantagethat it affects signal and noise equally.We have developed an adaptive method which treats signaland noise separately in each of several frequency bands.The spectral distributionof signal and statisticalnoiseIs estimatedby sequentiallyacquiringtwo equalâ€”countimages, octave bandpass filtering them with a series offlIterscoveringthe useful spectrum,and comparingcountsin correspondingpixels for each filtered imagepair. Ina noiseâ€”freeimageall correspondingpixels would haveidenticalcounts, while in a noisy image correspondingpixels have relativelyhigh count differences. From thesedifferences,the noise levelof the original compositeimage can be estimated in each portion of the frequencyspectrum. An amplitude threshold is set by each of thesenoise levelswhich mllows only informationabove the threshold to be retained in an image formed by suniningthe octaveâ€”filteredpair; in regions of this filtered, sumedimage where the signal is absent, statistical noise iseliminated, Becasue each filter bandwidth is one octave,

distortion products generated by the nonlinear thresholdingare outside the filter passband and can be removed with asecond octave filter identical to the first. Outputs fromthe second filters are summed to form a final image withreduced noise and without distortion Introducedby thethreshold. Images processed with this method have lessapparent noise than those processedwith simple lowpassfilters.

DOSIMETRY/RADIOBIOLOGY

RADIATION ABSORBED DOSE TO THE INJECTION SITE FROMINTRADERMALLY ADMINISTERED Xe-133. J.L. Coffey, Oak RidgeAssociated Universities, Oak Ridge, TN and M.J. Daly, VAMedical Center, Tucson, AZ.

Intradermally administered Xe-l33 has been usedsuccessfully to assess the skinâ€”capillaryperfusion inselecting amputation sites or for skin grafts and otherreconstructive procedures. We have estimated the radiationabsorbed dose to the injection site from this procedure toevaluate the radiation risk. Between 250 and 600 pCi(9.25â€”22.2MBq) is injected in 0.05 cc volume. Theactivity injected is determined by counting the syringebefore and after injection. The bolus of Xeâ€”133activityis known to displace the skin to some extent. We havecalculatedthe dose to the injectionsite for twodifferent situations. Case 1. The skin is totallydisplaced by the bolus of activity. Using the methoddescribed in Hine and Brownell, we calculated the dose to

the tissue at the surface of the activity. Case 2. Thebolus of activity is uniformly distributed in a tissuevolume of 0.22â€”0.52cc (based on the observation that theinjection site is 0.75â€”1cm in diameter and assuming aspherical shape). We calculated this dose by using theMIRD technique. The estimated absorbed doses to theinjection site from 400 pCi (14.8 MBq) are 84 rad (0.84Cy) in Case 1 and between 16 rad (0.16 Cy) and 38 rad(0.38 Cy) in Case 2. The absorbed dose to the organs ofthe body would be essentially the same as with IV injected Xeâ€”l33since the elimination from the injectionsite is usually quite rapid. (ORAl)operates under contractnumber DEâ€”ACO5â€”76OR00033with the U.S. Department ofEnergy, Office of Health and Environmental Research.)

PC-SULFUR AND AWrI?.5@NYCOLLOIDS AND IN-OXINE LABELED CRANULOCYTES : ARE THERE FUNCTIONAL DIFFERENCES? E .B.Silberstein, P.G. Hayfield, M. Sperbing, R. Harris, P. Hook.University of Cincinnati Medical Center, Cincinnati, OH.

Although indium-lbb oxine has been enÃ§boyed as a loukocyte label for over 5 years this radiopharmaceuticalstill has potential drawbacks: IND status; specialconditions for labeling not easily achieved in every nucbear medicine laboratory; labeling of and damaging lymphocytes when granubocytes are labeled, Several attemptshave been made to employ granubocyte phagocytosis tospecifically â€œselfâ€”labelâ€•with a radioactive particle.The obvious choice is conenercially available technetiumsulfur colboid (TcSC). A technetium antimony colloid(TCSbC) was also studied.

Granubocytes labeled with technetiumâ€”99m-antimony colloid had such poor chemotaxis that further testing was notwarranted. Chemotaxis with TcSC cells was mildly to moderately decreased. TcSC cells killed S aureus less wellthan In-wbc which performed this normally. Complementmediated phagocytosis was stimulated by In labeling whileit was subnormal in the TcSC experiments although stimubated by TcSbC. Peroxide production by In-wbc and TcSCcells was normal except for some stimulation in the restingphase at higher doses by In. Cells with both labels ingested uncoated latex particles and reduced NBT normally.

It is concluded that granulocytes labeled with indiumwith activities from 1â€”500uCi have essentially normalfunction in a series of tests not all of which have beenheretofore reported. Larger activity (2 mCi) of TcSCreduces some but not all of these functions. At the dosesemployed a major advantage of In is the 75% av. labelingefficiency while specific TcSC labeling was 12%.

RADIOBIOLOCICAL EFFECTS OF IN-lll ON LYMPHOCYTE, GRANULOCYTE AND PLATELET FUNCTION. E.B. Silberstein, P.G.Mayfield, M. Sperling, R. Harris, W. Bullock, P. Hook.University of Cincinnati Medical Center, Cincinnati, OH.

Estimates of the integrated dose per cell received byindiumâ€”lillabelled neutrophils and platelets have beencalculated at 1480â€”1750rads and 12,900â€”14,500rads rcapectively. Lymphocyte radiation doses are more difficultto estimate because of nonâ€”uniformityof nuclear radiation.tiehave undertaken functional and morphologic studies ofthe Inâ€”biblabeled human neutrophilic polymorph (poly),lymphocyte (lym) and platelet (plt) employing doses from2â€”500uCi of Inâ€”illoxine.

The lyn mitotic index is inversely correlated with activity of indiumâ€”lllemployed with r= â€”0.69,p <0.01.When more than 375 uCi Inâ€”illwere added there was morethan one aberrationper cell. T cell dependentB cellantibody formation was 10% of normal with less than 300 uCiIn. The following plt studies were normal: morphologyunder inverted phase contrast microscopy; aggregation withbovine and rat collagen; chemotaxis for collagen in a newsystem we have described which is more sensitive than anyaggregation test.

Poly function was normal for latex ingestion but withC3 ORO some stimulation of phagocytosis by In-lll oxinewas noted and confirmed with peroxide production. NBTreduction, chemotaxis and S aureus killing were normal.

Inâ€”lllin diagnostic doses causes marked functionaland chromosomal abnormalities of surviving lymphocytesand stimulates some granulocyte functions. Plateletfunction remains normal, Appropriate controls excludedan effect of oxine alone.

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PROCEEDINGS OF TIlE 28th ANNUAL MEETING

The various gamma camera system parameters for incorporation into the response function were determined expenimentally using 99mâ€”Tcand a tissue equivalent medium.These included: i) the geometric attenuation coefficient,ii) the medium attenuation coefficient, and iii)the spatialresolution as a function of tissue depth. Single photonemission data were acquired using a rotating phantom design which included various source strengths and geometricconfigurations.

The reconstructed images provided by the new algorithm(MFART) were compared with images reconstructed from thesame data using conventional algorithms such as ART andattenuated ART. The results show that the improved algorithm has achieved a more accurate image reconstructionproviding lower noise characteristics, improved spatialresolution, and the potential for reliable quantitativeanalysis.

NEUROANATOMICALâ€”PHYSICAL FACTORS AFFECTING QUANTITATIVEACCURACY IN POSITRON COMPUTED TOMOGRAPHY (POT). J.Mazziotta, M. Phelps*, D. Plummer*, D Kuhl*. UCLA Schoolof Medicine, Los Angeles, CA.

Partial volume effects in cerebral imaging using POTwere analyzed with repect to resolution. Volumes of alarge number of cerebral structures were determined fromanatomical atlases and compared with known or predictedPOT resolutions. For structures less than twice POTresolution a correction can be applied (method of Hoffmanet al) whereby actual tissue activity concentration can becalculated from the measured value. Knowledge of size andshape of particular structures allows such corrections.

An estimate of the degree that partial volume effectsoccur at various resolutions was obtained by digitizingimages of human brain slices and assigning uniform typicalvalues to gray, white and CSF structures. Images werethen smoothed by twoâ€”dimensional convolution with agaussian function having a FWHM from .5 to 2 cm. Valuesfor specific structures varied from their assigned valueas a function of partial volume effects with highestvalues in regions of high gray matter concentration (basalganglia). Largest errors occurred when small, irregularregions were located adjacent to structures whose activitywas significantly different from the selected region.These errors are minimized when (1) structures equal orexceed POT volume resolution element (voxel); (2)structures are oriented (tilting head or scanner gantry)so maximum number of voxels encompass object; (3)eliminating voxels along the structure's boundary, ar@ (4)comparing regions with similar degrees of mixing such ashomologous bilateral regions.

A DUAL TRACER TECHNIQUE FOR POSITRON EMISSION COMPUTEDTOMOGRAPHY (PCT). S.C. Huang, R.E. Carson, M.E. Phelps,E.J. Hoffman, D.E. Kuhl. UCLA School of Medicine, LosAngeles, CA

In nuclear medicine, dual tracer techniques are usedfrequently. For PCT, the usual method of separating twotracer radioactivities by energy discrimination is notapplicable because photons from pocitron emitters havesame energy (511 keV). We have thus developed a dualtracer techniquefor PCT that utilizes the differentdecayhalf lives to separate radioactivities of two positronemitters.

The technique requires each projection measurement of aPCT scan to be taken repeatedly in time, and these repeated measurements are fitted by a 2â€”exponentialfunctionA EXP(â€”at)+BEXP(â€”bt),where a and b are the physical decayconstants of the isotopes. Values of A and B are respectively amounts of radioactivities in the projection due totracers. By substituting the estimated values of A (or B)for the projection measurements, the distribution of tracer1 (or 2) can be obtained by regular PCT reconstructions.The technique has been tested on phantom studies with ECATscanner and has been found to be successful.

In one set of studies, a phantom was filled with twoisotopes in separate compartments. The technique recon-structed the individual distributions correctly. In anothen set, transmission and emission scans were taken simultaneously. The technique succeeded in giving isotope distnibution and attenuation coefficients of phantom.

In conclusion, the dual tracer technique for PCT has


INSTRUMENTATION

AN ITERATIVE ATTENUATION CORRECTION FOR A SINGLE PHOTON,SCANNING, MULTI-DETECTOR TOMOCRAPHIC SYSTEM. S.C MooreJ.A Brunelle and C.M Kirsch. Harvard Medical School,Boston, MA.

A new iterative attenuation correction has been developed for a single photon, whole body emission tomographicsystem using 10 scanning detectors in a circular geometry.The algorithm is similar to other iterative schemes, inthat it minimizes the difference between the measured projection data and each iteration's estimate of the projection data. However, due to the two-dimensional scanpattern and geometric line source response, the estimationof projection data from an assumed or measured attenuationmap is more complicated than, for example, a rotatinggamma camera system with a parallel hole collimator.

The image reconstruction program used up to now contamed a simple multiplicative attenuation correction.This provides only an approximate correction for the caseof spatially extended source distributions of varying concentration. The programshave been tested using thefollowing physical phantoms: a 20 cm diameter cylinderwith two 5 cm vials of higher Tcâ€”99mconcentration; a 35cm diameter cylinder with a 5 cm inoveable vial of higherTcâ€”99mconcentration in different positions; a human torsophantom containing a stationary heart phantom with Tl-201.For all vials larger than the system's spatial resolution,the iterative attenuation correction provided a veryaccurate measurement of concentration ratios, in contrastto the simple multiplicative correction. Using thesephantoms, absolute dose calibration is also demonstrated.The heart phantom results indicate that organ volumemeasurements are more accurate after the iterativeattenuation correction.

QUANTITATIVE NMR DETERMINATION OF SPATIAL VELOCITY INFLOWING MEDIA. L.P. Clarke, R.A. Devine, W. Sattin, andA. Serafini. University of Miami, Miami, FL

The purpose of the study we present here is to demonstrate the potential application of NMR to blood flowmeasurements. It is demonstrated that detailed quantitative or qualitative information may be obtained on bothspatial velocity variation (i.e. laminar versus turbulentflow), arterial wall elasticity, and other characteristicsof blood flow not readily accessible via more commontechniques such as Doppler Ultrasound, Radiotracer techniques, etc. The feasibility of NNR applied to very lowflow rate systems, i.e. plants, has been clearly demonstrated by Hemminga and de Jager (1).

Conventional pulsed NMR has been used at low frequendes (4MHZ) on a laboratory system simulating both theflow rates and characteristic relaxation times of protonsin arterial blood systems. Results obtained suggest that,although flow effects can be clearly observed, sensitivity is inadequate at such low frequencies. Preliminaryresults for higher frequency (@â€˜28MHZ)are presented andproblems, both experimental and theoretical, involvedin their interpretation discussed.

1. M.A. Hemminga and P.A. de Jager, Journal of Hag.Resonance 37 ;â€”16,1980

DEVELOPMENTAND EXPERIMENTAL EVALUATION OF AN IMPROVEDSINGLE PHOTON ECT RECONSTRUCTION ALGORITHM. T. Yoshizumi,S.R.Thomas, W.C.Wee, J.C.Kereiakes, and D@R@ Jones. University of Cincinnati, Cincinnati OH

An improved single photon emission computerized tomographic (ECT) reconstruction algorithm has been evaluatedexperimentally using a gamma cameraâ€”computersystem. Thealgorithm provides: a) direct correction for attenuationand scattering; and, b) compensation for the gamma cameraresponse characteristics through direct incorporation ofthe point spread function (PSF) as a function of depth inthe tissue. The correction technique involved introducinga mathematical system response (distortion) function intothe generalized projection equation and deriving a closedform solution for its Fourier transform. Image reconstruction is accomplished using a Modified Fourier AlgebraicReconstruction Technique (MFART).



PROCEEDINGS OF THE 28th ANNUAL MEETING

high potential for examining two physiological functionssimultaneously and for eliminating motion and alignmentproblems in performing attenuation correction in PCT.

LONG AXIS ALIGNMENT IN COLLIMATOR TOMOGRAPHYOF THE HEARF.w Chang S.L Lin and R.E.Henkin. Loyola Univ. Med.Center, Maywood, IL.

Due to the discrete, symmetric and limited data sampling in 7â€”pinhole(7PM) and quadrant slant hole (QSH) colbimatortomography,both techniquesare limited to cardiacimaging.

The effect of misalignment of the long axis of the leftventricle (LV) with respect to the axes of symmetry indata sampling, was investigated with phantoms simulatingthe heart on a QSH collimator system. A phantom with nodefect was imaged with its long axis tilted 0Â°,10Â°and20Â° from the collimator axis. The tomograme reconstructedfrom the 20 tilt acquisition showed a remarkable defectopposite from the direction in which the collimator wastilted. The 10Â°tilt acquisition did not create significant artifacts. The 7â€”pinholecollimatorbehaves similarly under the same set of test conditions.

When correlated with the raw images acquired, one caneasily identify artifacts caused by misalignment from thedifferences in elongation of the phantom analog image indifferent quadrants.

In patient positioning as a preventive measure, oneshould align the long axis to the left ventricle to bewithin@ 10 of the collimator axis. with this constraintin mind, it turns out that simultaneous viewing of theheart from four orthogonal projections is necessary toachieve the proper alignment of axes. However, differences in tissue attenuation among the multiple views increased as a result of the requirement of alignment. Theoretically, the attenuation problem can be satisfactorilyresolved based on a model of tissue distribution.

EFFECI OF POSIflONINC ON DETECIION OF MYOCARDIALPERFUSION A@CRMALITIES BY THE @TXrIP1SLANT HOI.ECOLLIMATOR. 0. Ratib, E.Henze, H.R. Schelbert. IXLA Schmol of Medicine, ths Angeles, CA.

Tim rotatir@ slant bele collimator (RSH) has recently beenproposed as an alternate approach to limited angle tomography ofthe heart . To evaluate its usefulness for myocardiab perfusionscanning,@ measured its resolution axI characterized its basicperformance in 20 phantom studies atsi in 5 normal individuals.Axial and planar resolution wre first measured uai@ a 0.9 meline sot@ce at several depths. Tban a myocardial phantom with adefect variable in size, location ar@ isotope concentration @simaged in tba three conventional planar views, and with the RSHperpemlicular to its boi@ axis as well as with a 30Â° tilt inorder to simulate the trua imagir@ conditions in men. The imagesware analyzed from regions of interest (ROI) arid with circusferential profiles (cPA) arsi tba sensitivities of both metlxdscompared. By tiltir@ ttm phantom, a predictable relative defectin tba inferoapical wall with 23% coomt rate (cR) reduction dueto a partial voluseeffect becauseof obliqueslicing wasdesonstnated. Further, because of diminished adjacent count contnibution a second artificial defect was moted in the anterobasalportion with 2l.@ @R reduction. Tba smallest, significantlydetectable isotope free defect was 5 cc in size , while 10 cc sizedefects mere detectable only when isotope concentratiorm warereduced by more than 502. Anterior wall defects were signif 1â€”cantly better visualized than those of tbe posterior wall (by19. St) . Using CPA, defect detection from RSH tomographic Imageswas superior to conventional planar imagir@ by a factor of 1.8.Artifacts observed in phantoms ware confirmed in our sttxiiesofnormal iodividuals. We conclude that, under idealized conditions, imagingwithRSHis superiorto planarimaging.However,because of frequent inability in positioning the RSH penpendicuber to the long axis of the left ventricle in patients, RSH canprod@e artefactual perfusion defects.

QUANTITATIâ€•E.\UTORADIOCRAPHY WITH RADIOPHARMACEUTICALS.P.Som, M.Meyer, A.B.Brill, F.H.Oster, Y.Yonekura, J.A.G.Russell, I.Fand, W.McNally, C.Arnett, A.Findley, J.Fowler,R.MacCregor, A.Wolf, Brookhaven National Laboratory,Upton, NY, and SUNY at Stony Brook, NY.

The increasing use of medical cyclotrons and PETT willrequire the design and development of new radiopharmaceu

ticals that can provide quantitative metabolic informationin normal and diseased conditions.Double tracer studiesare highly desirable for delineating the behavior of theradiopharmaceutical in relation to the appropriate reference compound. This has been accomplished by bargesection macroautoradiography in conjunction with a com@+putenized videodensitometer with special reference to 8emitting nadiopharmaceuticals. Initially, studies werecarried out with different types of xâ€”rayfilms to determine the relative quality of autoradiographs for quantitation of radiotracens emitting soft betas and positrons.With stepâ€”wedgeFâ€”18standards, the response of SB5 xâ€”rayfilms was found to be linear for a range 250â€”2500Bq/cm2.Studies were carried out with F-18â€”fluorodeoxyglucose todetermine the regional glucose metabolism in large andsmall laboratory animals under different conditions. AutoradioÃ§Ã§raphsof coronal section of sheep brain provide muchhigher snatial resolution than can be obtained by inâ€”vivoPETT imaging. Autoradiographs of whole body sections ofmice with and without a treatment with chborpromazine(CPZ)were significantly different. CPZ greatly reduced thetissue uptake of radioactivity (except the heart) reflecting low glucose utilization in the sedated state. Thistechnique is an important advance in the design and theevaluation of new radiopharmaceuticals.

DIGITAL GAMMA CAMERA PERFORMANCE CHARACTERISTICS. J. R.Penny, R. H. Johnston, J. R. Hodge, S. A. Woodard, andV. H. McCartney. University of North Carolina, Chapel Hill,NC.

With the advent of cardiovascular nuclear medicine camea new demand for a higher count rate capabilityfrom Angertype games cameras. New games cameras that incorporatethreshold discrimination and other electronic techniques toshorten dead time provide typical count losses of 20% atcounting rates of 25K and 30K cps. This corresponds to adead time of 6 to 7 psec as measured by the two sourcemethod in a scatter phantom. A new coimnercially availableunit utilizing digital circuitry is claimed to show improvement in count rate capabilities with preservation ofspatial resolution. A comparison of a typical contemporaryhigh resolutiongames camera and a new stateâ€”ofâ€”theâ€”antdigital gamma camera will be presented. The performancecharacteristics measured were: the system dead time detenmined with the Adams cardiology phantom, intrinsic countrate performance according to NRMA standards, and spatialresolution (YWUM, FWTM and MTF) with and without scatterand as a function of count rate. System sensitivities werealso compared for bow sensitivity/high resolution, generalpurpose and dynamic collimators for each camera.

DISTORTION INTRODUCED IN RADIONUCLIDE CAMERAVIEWS BYMULTIFORNATIMAGERS. W.L. Dunn, M.L. Brown, Mayo Clinic,Mayo Foundation, Rochester, MN, M. Tuscan, University ofMichigan Hospital, Ann Arbor, MI.

Multiformat imaging systems for displaying radioisotopiccamera images on standard xâ€”rayfilm are coninonlyused innuclear medicine departments. This study has investigateddistortions in scintigraphic images caused by the imagen.

The degree of spatial distortion of radionuclide cameraimages is compared in six different cameras. The magnitudeof the distortion was determined by imaging circular beaddiscs placed on the camera's parallel hole collimator.Single format views of the discs were then examined formeasurable distortion of the circular objects.

The instruments tested were the Ohio Nuclear 110and 4105, Searle Pho Gamma LFOV, and the General Electric400T. We found image nonlinearity variations of 4 to 25%.In order to determine if the distortion could be due tothe camera's detection system, the imager was bypassed andviews of the discs were recorded on Polaroid film and witha computer. Nonlinearity was not more than a few percentin both cases. We feel this illustrates the need forindustrialstandardsapplied to imager spatial distortionperformance.

OBJECTIVE EVALUATION OF VIDEO CASSET'FE MID RECEIVER/MONITOR SYSTRMS. M.W. Vannier, R.N. Beibn*, S.R, Yonts*,and F.M. DeLand*, Mallinckrodt Institute of Radiology,

P66 THE JOURNAl. OF NUCLEAR MEDICINE




St. Louis, MO.and University of Kentucky Medical Center*,Lexington, KY.

Vidâ€¢orcceiven/monitor units are ubiquitous elements ofmodern nuclear medicine computer systems. Objectiveevaluation of video receiven/momitor systems characteristicably requires test equipment which is complex, expensiveand generally unavailable in nuclear medicine departments.An objective evaluation of a variety of video receiver/monitor systems was performed using a 3/4â€• helical scanU.-matic cassette video tape containing a sequence ofprecision recorded test signals and images, developed bythe Society of )4otion Picture and Television @gineers(SMPTE) . The color video tape recording contained grayscale, color bars, video amplifier frequency response,indoor and outdoor color scenes, safe action and titleareas, as well as grid and dot patterns (for size,linearity and convergence adjustments).

I@nour evaluation of color and monochrome video monitors,multiformat video cameras end videocassette recorder/player units (used for nuclear cardiology), we foundsignificant misadjustments or electronic malfunctionsin all units tested,

This S)@TEtest videocassette tape is a valuable tool forquality control and objective evaluation of nuclearmedicine video receiver/monitor combinations.

A SEMI-AUTOMATEDQUANTITATIVEQUALITYCONTROLSYSTEMFORGAIIMACAMERASUSING PAPER-BACKED PRINT AND TRANSPARENTFlU! TEST IMAGES. H.V, Piltingsrud, R.G. Hoops andM.R. Blizzard. FDA, Nuclear Medicine Laboratory, BEN,University of Cincinnati, Cincinnati, OH.

Past efforts at the routine evaluation ef theperformance of gamea cameras using final product imageshave resulted in primarily qualitative assessments of thevarious performance parameters. This paper describeswork accomplished in developing a system for quantitativeby determining certain performance parameters of gammacameras using paperâ€”backedprint and transparent filmtest images of the same type used for viewing by thenuclear medicine physician. By use of appropriate transmission and lineâ€”sourcephantoms, the gamma camera'sspatial resolution, uniformity and linearity, as afunction of position in the image field, are determined byuse of a seniautomated image scanning and data reductionsystem. This system consists of a high resolution scanning microdensitometer, interfaced to a computer, alongwith necessary programs to locate bar and line gridintersection points in the image. Also included arealgorithms for calculating the various image parametersdesired. Results of the system's analysis of theperformance of several gamma cameras will be presented.It appears that this system provides a practical methodfor quantitatively assessing the performance of largenumbers of gamma cameras using the finalâ€”productimagesfrom the cameras. The potential use of this method inconducting a large scale survey of gamma cameras will bedescribed.

EFFECT OF OBJECT VOLUME ON QUANITATION WITh ECAT II.RN Kessler, J.Bird, A.E. Jones, and G.S. JohnstonNational Institutes of Health, Bethesda MD 20205

The effect of object volume on recovery of quantitativedata in a positron tomographic system, the ORTEC ECAT II,is examined in the present study. Hoffmanetab; haverecently studied the effect of object size upon recoveryof quantitative data is one and two dimensional systemswith hot test objects â€”either bars or cylinders â€”and acold background. In the present study the effect of partial voluming in three dimensions using spherical phantomsis examined under varying conditions â€”hot spheres with acold background, cold spheres with a hot background, andhot spheres with a warm background at varying ratios, Usingthe medium resolution scan mode and medium resolution cobbimators for the ECAT II, this being the mode most commonlyused at our institution in clinical studies, the maximal(hot spot) or minimal (cold spot) recoveries were obtainedwith hot and cold spheres of various diameters.

Nominal Sphere Size Maximal Recovery(Hot Sphere)

3.15 cm 0.732.20 cm 0.421.70 cm 0.271.25 cm 0.11


____________________MinimalRecovery__________ (ColdSphere)

0.120.300.490.68

Results for hot sphere with a warm background at varyingratios are presented and discussed in relation to systemresolution. The relationship of system resolution toquantitation and its effect upon the ability to quantitateisotope concentration in relevant cereberab structures isdiscussed.

@ETTOMOGRAPRIC IMAGING OF NITROGEN-b3 IN THE HUMAN HEART,PANCREAS AND LIVER. W.G. Myers, R.E. Bigler, A,S. Celbard,R.S. Benua, M.C. Graham, and J.S. Laughlin. The MemorialSloanâ€”KetteringCancer Center, New York, NY.

We use the first connnencialbyâ€”fabnicatedversion of theNCR â€œpositron cameraâ€• to image simultaneously the distributions of 10â€”mmNitrogenâ€”l3in the heart, pancreas, andliver of normal human volunteers after i.v. enzymaticablysynthesized Lâ€”(Nâ€”b3)glutamate.The instrument routinely isused to make coronal, 2â€”dimensional,tomographic, focalplane longitudinal images by means of the backâ€”toâ€”backSllâ€”keVÂ±yq@ta pairs emitted at 180+0.3 degrees. Theseimages include a reference overlay index of the positionsof the transaxial images made successively when the instrument is operated in the 3â€”dimensionalmode. As many as 23transaxial images then are made simultaneously of â€œslicesâ€•1 cm thick (FWHM), at 1.4â€”cmsequential spacing. Fivetransaxiab image slices made through the heart, in a distance of 6.6 ass, revealed Nâ€”b3had concentrated chiefly inthe myocardium of the left ventricle and interventnicularseptum. Three transaxial images made through a pistolshaped pancreas, in a distance spanning only 3.8 cms,clearly showed high concentrations of Nâ€”l3separatelyin the head, body, and tail of the organ.

In addition to studies with Lâ€”glutamate,Lâ€”valine,andother amino acids labeled with Nâ€”b3,the instrument also isadvantageously useful to assess the distributions in two orthree dimensions of Fâ€”b8on Câ€”lbin bone cancers, and Kâ€”38in the myocardium of dogs, monkeys, or human volunteers.

We use it also to study dynamic biochemical/physiologicprocesses with these shortâ€”livedpositron emitters. Wegenerate them with our isochronous, 4â€”particlecyclotron;and then propel them pneumatically 170 m in 40 a beneathE. 68th Street to the nuclear medicine suite.

A t@W SIOHAL AMPLIFICATION TEQINIQUE R@RI1@ROVI@ RESOLIYrIONINPOSIT@N @@1Ph7r@TO@APHY (POT). M.E. Phelps, S.C. Huang,E.J. Hoffman, D. Pluisser, D.E. Kuhl. UQ.A School of Medicine,Los Angeles, CA.

Computed tomography (CT) is a metbesatical techniqueproviding qtmntitation of local variables. However, the emormousnusber of anittmetic operations and high spatial frequencyamplification produces high image noise and a inverse third powerrelationship between image resolution (R) and image counts, N. Ris determined by linear and angular sampling, reconstructionfilter function (F) , N and intrinsic detector resolution (TA).Importance and limitations of IA haven't been stressed in Cr.Normally sampling and F are selected so R@ lit to yield highestimage resolution. However, an appreciation that both II and Phave high frequency amplification capabilities and that theformer can provide this witheut increasing noise, lend us tostudy this approach for Improving R in POT. Simulatedrecorwtnuctions of bar phent@im with IRâ€•12,9,6 and 3. San and thesame F (standard F for 12mm reconstructions) progressivelyimproved image resolution fran 13 to 5.6mm with no increase innoise. Alternatively, with the same sampling and N, dramaticnoise reduction wa@sachieved with small IR by lowering cutofffrequency of F while still providing good image resolution (12and 3 . @snItt required about @1and 8O(@ccounts, respectively toachieve R'@l2.2asn with 10% std. dcv. noise). Simulatedreconetructions fran actual brain slices and experimental studieswith TA from 18 to 3.5 ma were performed to further demonstratethis approach. This signal asplification technique with small IRcan be achieved with small BQ) detectors and offers dramatic POTresolution Improvement or noise reductions for dynamic studies atsomewhat lower R (i.e. 12 to 16mm).




PRELIMINARYCHARACTERIZATIONOF THE PROPERTIESOF A TRANSAXIAL WHOLE-BODYSINGLE-PHOTONTOMOGRAPH: EMPHASISONFUTURE APPLICATIONTO CARDIAC IMAGING. D.L. Williams,J.L. Ritchie, G.D. Harp, J.H. Caldwell, and G.W. Hamilton,VAMedical Center and University of WashingtonSchool ofMedicine,Seattle,WA;andR. Eisner,0. Nowak,andJ. Leon, General Electric Company, Milwaukee, WI.

Detectorand gantry alignmenthave been studiedon aGeneral Electric400T ECT system,with a 40 cm diameter,37 PMTMaxiCameraIIdetector.At a 20 cm radius-ofrotation,point-spread-functionFWHM was 17.2 sinwith ahigh-resolution, parallel-hole collimator. Point sourcemeasurementsof the mechanical center-of-rotation, whichaligns projectiondata with respect to the reconstructionmatrix, had an RMS deviationof 0.24 m as measured from16 pairs of opposingviews covering 3600 of detector rotation. Axial variation (i.e., head-to-feetdirection)ofthe mean center-of-rotationvaried by 1.1 m standarddeviation,based on seven independentpoint sourcemeasurements which covered the axial range of the detector fieldof-view. MaxiCamera II detector alignment parallel to theaxis-of-rotationwas determinedfrom 32 views covering3600 of gantry rotation of a point source located 12 cmoff the axis-of-rotation. Analysis of the resultingaxialâ€œsinogramâ€•indicatedan RMS deviationo@ 1.4 sin,whichimpliedan angular misalignmentof 0.16 . In total, thesemeasurementsindicatedthat critical gantry alignmentswere within a fractionof the spatial resolutionFWHM inair and v@uld not be responsiblefor resolutiondegradations or artifacts in the reconstructedimages.

SINGLE PHOTON EMISSIONCOMPUTEDTOMOGRAPHYOF LIVER AND

BRAIN WITH A ROTATINGGAMMA CAMERA.

H.J.Biersack,R.Knopp,andC.G.WinklerInstitutefor Clinicaland ExperimentalNuclear Medicine,Universityof Bonn, West Germany

Single photon emissioncomputed tomography(SPECT)of liverand brain was performed in a total of 246 patients. In 116patientsSPECT of the liver was done in additionto conventionalcamera scintigraphy.51 patientsrevealedpathological findings (focal liver disease:n = 20, diffuseparenchymaldamage: n = 31). In 11 cases with focal liverdefects diagnosticaccuracycould be improvedby SPECT, in2 patients,however, smaller defects (1 cm) were only visualizedby conventionalcamera images.Eight patientswith proven normal liver but equivocalconventionalscanrevealedtruenegativeSPECTresults.

In another 130 patientsbrain scintigraphywas performedusing camera scintigraphyand SPECT. Six of these patientshad brain lesions,2 of them sufferingfrom hemorrhageand4 from tumors. Two of these 6 lesions (1 hemorrhage,1basal brain tumor) could only be detected by SPECT.

In conclusion,our results in liver and brain scintigraphyshow that diagnosticaccuracycan be considerablyimproved by emission computed tomography.Conventionalcamerascintigraphy,however,with its better resolutionin smaller peripherallylocated defects (about 1 cm) should beadditionallyperformed in any event.

Ta@KhGRAPHICIMAGINGOF THE CHEST USIP@ @DMPT0NSCATr@ING AND Ir192 SO(RGES; PfltFOIB4AN@EANDATr@JUATIONCDRRECflON. RiccardoGuzzardi, Marghenita Zito, Maurizio Mey. C.N.R. Institute ofClinical Physiology. Via Savi 8 56100 Pies, Italy.

The original technique of 90 degree Compton ScatteringTomograpby for imaging the density of chest sections with thegamma camera has been described (J Mud Med All Sci 22, 1:11,1978) and evaluated (Phys Med Biol, Jan 1980, in press) using alinear distribution source of Hg-2O3. T@ major limitations warefound: a) the maxitmsnactivity of the source was 1.5-2 Ci; b) the47 day half-life Hg-2O3 solution required frequent and unsafeloading. To overcome these limitations and to improve furtherthe methedology, a new approach was developed with t@ pointsources of Ir-l92 (75 day half-life), 40 om apart and with 20 cmcollimation. This provides: a) a reduction in acquisition timefrom both higher pheton yield and high specific acitivity of 192-Ir. Using 1 Ci of activity, the improvementis 1.6 over Hg-2O3;b) simultaneous detection of t@ 90 degree scatternd peaks (191keV and 245 keV). This allowa formation of a second scatter

image for attenuation correction; c) since this appreoch usessealed point sources radioprotection problems in source preparation are overcome. A significant improvement in the Cou@tonImaging was obtained with an algorithm for the correction of bothprimary and secondary scattered beam. The correction actsthrough: a) detection of the regions with a constant attemoationcoefficient by means of an edge detection algorithm; b) calculation of the attersiation coefficient in each region of uniformattenuation; c) attenuation correction of each region using itsown coefficient. The scattered beam is corrected with scatterimages at tia@energies. The combined use scatter and SinglePheton Tomugraphy using rotating gamma cameras could help in theattenuation correction of the emission images of tie chest andprovide the therax density distribution using the same detectorgeometry.

RADIOIMMUNOASSAY

AN INTERLABORATORYNEONATAL THYROID SCREENING PROGRAN.J.R.Hansell, Veterans Administration Hospital, Philadelphia, PA

The College of American Pathologists (CAP) distributedin 1980 three dried blood spot specimens to 50 laboratoriesin 19 states and Canada. The three samples were prepared bythe Center for Disease Control. Concentrations of hTSH andthyroxine were adjusted so that three clinical neonatalconditions were simulated: euthyroidism(A), primary hypothyroidism(B), and secondary or tertiary hypothyroidism(C).

Participants were asked to submit their method, resultsand clinical interpretation. Eleven methods were used toassay thyroxine, five for hTSH. There was a greater divergence in concentrations obtained in assaying the two anabytes when using a dried blood specimen in comparison tothose methods using series. The precision of the former waspoorer than the latterwhen comparedat concentrationsofsimilar magnitude (CAP Basic Ligand Survey, 1980).

Only one laboratory incorrectly diagnosed the euthyroidstate of sample A; and one, the hypothyroid state of C.Eight to 15 laboratories chose not to classify one or moreof the samples. Nineteen participants, though correctlyspecifying the hypothyroid state of samples B and C, didnot differentiate its type. In all cases but one, wherein

participants chose not to classify any clinical conditionor subclassifyhypothyroidism,the laboratorydid not perform the hTSH assay, accounting for their incomplete response.

The study suggests that despite disparate assays obtamed for hTSH and thyroxine, laboratories performingboth assays were able to correctly differentiate euthyroidism from hypothyroidism.

CLINICAL EXPERIENCE WITH A NEW DOUBLE ANTIBODY RADIOASSAYFOR SERUM THYROGLOBULIN. M.A. Schwartz, W.H. Bbahd, W.A.Baumgartner, J.S. Sangha, and I.V. Sultanian. VeteransAdministration Wadsworth Medical Center, Los Angeles, CA.

The value of serum thyrogbobulin (IC) levels in thyroidcarcinoma was determined using a new double antibody radioassay (Nuclear Medical Systems, Inc.). Serum bevels of TGwere correlated with clinical status in 38 patients withthyroid carcinoma. Three patients with detectable antibodies to IC were excluded from analysis. The results aresummarized below:Disease IC LevelsStatus Very Low Detectable High

(0â€”15ng/mb) (15â€”40ng/ml) (Over 40 ng/ml)Active 3 5 6Inactive 23 8 4Thyroid Remnants 4 1 4Several patients had multiple samples drawn, e.g. , beforeand after thyroid was discontinued, before and after bovineTSH stimulation, and before and after thyroid surgery.

Most patients with inactive thyroid carcinoma have verylow levels of IC. However, not all patients with activedisease have high levels. Individuals who have postsurgical thyroid remnants may have levels of IC ranging fromvery low to high. Diagnostic intervention changes IClevels. In 2 patients, IC levels went up after thyroid wasdiscontinued and scan data revealed abnormal uptake. Inboth cases, serum 1511showed a concomitant increase. Overall, there is a suggested correlation of ISH levels and IC

P68 TIlE JOURNAL 01: NUCLEAR MEDICINE




levels after thyroid hormone is stopped. However, additional patients should be studied before this relationshipis established.

Serum IC is a useful followâ€”upmeasure in athyreoticpatients with thyroid carcinoma.

INHIBITIONOF T4 RELEASE BY ENDOTOXIN-INDUCEDFEVER. M.K.Elson, M.M. Oken and R.B. Shafer. VA Medical Center,Minneapolis,MN.

We have previouslyreported the effects of fever andhyperthermiaon thyroid function. Using a rabbit model,we demonstrated a rapid reduction in serumT3 and a reciprocal rise in reverse T3 following endotoxin-induced fever,that did not occur with hyperthermia. Serum T4 levelswere significantlyreducedwith endotoxinfever and showeda reboundabovebasallevelsat 24 hours. No similareffect was seen with hyperthermia. These results raised thequestionof whether the rapid alterationin thyroid hormonelevelswas relatedto increasedhormoneexcretion,reducedhormoneproduction,or both. To answerthisquestion,we injectedrabbitswith high specificactivity125I-T3and1251-T4,inducedendotoxinfeveror hyperthermia and compared levels of activity at 2, 4, 6 and 24hours to those of controls. Results showed no significantdifference in excretion of 125I-T3 betweenendotoxin fever,hyperthermiaand controls. Similarly,there was no significant difference in excretion of 1251-14 between endotoxin fever, hyperthermiaand controls,except at 6 hoursbetween endotoxin fever and hyperthermia(p>O.O5). Weconclude that the rapid decrease In serum T@ and reductionin serumT4 foundwithendotoxin-inducedfeveris likelyrelated to transientinhibitionof 14 release. This inhibition appears unique to endotoxin-inducedfever and isnot related to increasedbody temperatureas shown by lackof effect of hyperthermiaon thyroid hormone levels.

THE PREVALENCE OF UNSUSPECTED AUTOIMMUNE THYROID DISORDERS.V.T. Kung, P.M. Weber, and L.V. dos Renedios. KaiserPermanente Medical Center, Oakland, CA.

We have shown (Arch Intern Med lI@O:lOl@5,1980) that thefree thyroxine index (F'fi)can costâ€”effectivelylocatecases of unsuspected thyroid dysfunction, and we foundhyperthyroid prevalence of O.3l@ and hypothyroid prevalenceof 0.50%. Because many patients had antithyroglobulin(antiâ€”Tg) or antinicrosomal (antiâ€”N) antibodies in theirsera, we used these radioimnunoassays to determine theprevalence of unsuspected autoirninune thyroid disease inasymptomatic patients having a multiphasic health examination. Using our newly developed, highly sensitive assaysfor antiâ€”Hand antiâ€”Tg(Clin Chem 26:961, 1980), we testedthe sera of 986 patients @3Oyr (53% female). Patientsalso completed health assessment and special family historyquestionnaires and had FrI and TSH tested; other teats wereperformed as indicated. One or both antibody levels wereelevated in i8o (18.3%) (78% female). Among all subjects,i.6% had elevated TSH compared to 21.5% of those with antibodies (19% female, 31% male). Of these, all men wereeuthyroid, whereas 17% of women were not: 2/3 had hyperthyroiditis and 1/3 were hypothyroid. Of women withthyroid dysfunction and normal TSH levels, 2/3 were hyperthyroid and 1/3 hypothyroid. Preliminary data suggestthat the many euthyroid patients who have elevated TSH andantibodies are at risk for developing clinical hypothyroidism and should thus be closely followed.

RADIOPHARMACEUTICALS

UPIAKE OF RADIOCOLLOID IN VITRO BY MACROPHACESAND TUMORCELLS. K. Nagai, Y. Ito, N. Otsuka, A. Muranaka, I. Kaji,and Y. Kajihara. Kawasaki Medical School, Kurashiki, Japan

The mechanisms of absorption of colboid into the lymphatic capillaries after passing through the connectivetissue and deposition in lymph nodes remain elusive.Keeping lymphoscinti.graphy in mind, we carried out theexperiments related to deposition of radiocolboids in ratperitoneal macrophages(M4) and HeLaS3 in vitro. lechnetiumâ€”99mâ€”colboidsused were 3 kinds of Antimony Sulfide

Colloids(Uâ€”ASC,U.C.C., Mâ€”ASC,Mallinckrodt., Hâ€”ARC,Houseproduct), Sulfur colloid(Icâ€”S,CIS), Rhenium colboid(Icâ€”Re,CIS), Tin colboid(Icâ€”Sn)and Ca2+phytate(Phytate). Thecontact time of colboids with cells was 1 hr. The degreeof uptake of colloids by M4 increased proportionally to anincrease of cell numbers and dose of colloids administered.When radiocolloids were given in a concentration of 1 uCi/miâ€”medium,phagocytic activity of 1O6M4(% uptake/dosegiven) was the highest in Icâ€”Sn(14%)and almost the samein ABC group(5%). Next in order of the activity came Icâ€”S(4%), Phytate and Icâ€”Re. HeLaS3 took up 2.3% of Icâ€”Sn,0.22% of Hâ€”ABC.0.18% of Icâ€”Sand 0.03% of Icâ€”Re. Surfacecharge of all the colboids except Icâ€”Snwas negative.Electron micrographs revealed that ARC group and Icâ€”Snwere spherical, ranging 2.5â€”2Onm,70â€”80mmrespectively.Icâ€”S and Icâ€”Re were nonuniform, ranging 10â€”40mm, 3â€”l5nmrespectively. We conclude: 1) Surface charge and size ofcolloid contribute to the deposition of colloids in M4 andHeLaS3. 2) The degree of deposition in M+ is higher thanthat in HeLaS3. 3) Icâ€”Sndeposits to a higher degree inM@, however, it should be kept in mind that the bargeparticleâ€”sizedcolboid has a drawback being slow forabsorption into the lymphatic capillaries.

GHEMICALLY DESIGNED 99m-Ic RADIOPHARNACEUTICALS FOR THETUMOR DIAGNOSIS : 99m-Tc-DMSA. A. Yokoyama, N. Hata, H.Saji, K. Honiuchi, H. Tanaka, R. Monita, and K. lorizuka.Faculty of Pharmaceutical Sciences and School of Medicine,Kyoto University, Kyoto.

As previously reported, in vitro studies with somepobynuclear complexes of 99mâ€”Ic, such as citrate, DMSA andpyrophosphate have shown higher tumor cell accumulationthan 67â€”Gaâ€”citrate.In vitro studies with Ehrlich tumorbearing mice, 99mâ€”Icâ€”DMSAhas shown the highest tumor/bloodratio (1).

In this paper, a new approach on technetium chemistrywas applied for the development of a 99mâ€”Icâ€”DMSAcomplexwith affinity for tumor cells. An equilibrium between astable form of Ic(V)â€”DMSAand a dissociated form of the anion TcO43, structurally analogous to PO43 is postulated.DMSA having an cz,@â€”dimercaptogroup in the molecule, holdsconsiderable ability for the coordination of IcO43@ as astable complex; its integrity while in the blood pool willenhance the cell uptake, in the presence of membrane transport feature and retention mechanism.

The 99mâ€”Tcâ€”DMSAcomplex displaying those charactenistics was prepared at high pH of 8.0â€”8.5in the presence ofstrictly controlled amount of the reducing agent, SnC12, soas to achieve a complex of DMSA coordinated with Ic (V).Tumor/blood ratio of 3.7 and 6.0 was obtained at 3 and 24hrs post injection. An excellent contrast in scintigraphicimages was obtained as the blood pool activity was reducedby the administration of Fe(III)â€”NIAand ascorbic acid 30mm after the injection of 99mâ€”Icâ€”DMSAin rabbit bearing

@2tumor.

(1) A. Yokoyama and H. Saji: In Metal Ions in BiologicalSystems, Vol 10, Marcel Dekken, New York, Baseb (1980).

CHARACTERIZATION OF Tc-99m-BONE AGENTS (MOP, EHDP) BY REVERSE PHASE AND ION EXCHANGE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY. S.C. Srivastava, D. Bandyopadhyay, C. Meinken,and P. Richards, Brookhaven National Laboratory, Upton, NY.

Many Tc-99m radiopharmaceuticals,in particular the diphosphonate bone agents, are complex mixtures and not single homogeneous compounds as often indicated by routine qualitycontrol methods. This study was undertaken to separate andcharacterize the various components present in clinicallyused Tcâ€”Snâ€”MDPand Tcâ€”S@â€”EHDPpreparations by high performance liquid chromatography (HPLC) using radioactivity detection mode. A number of solvents and columns (anion cxchange (AE), Câ€”2, Câ€”8, and Câ€”18reverse phase (HP), N112â€”andCNâ€”bonded HP, etc.) were evaluated to obtain optimum separations. AR using an acetate buffer provides fair resolutionof the EHDP system but not of the MOP system. In contrast toAE materials, HP materials are very versatile, provide cxcellent resolution, and allow for repeated solvent changesfor arriving at optimum separation parameters. IcO4 isbound tightly to the AR columns but can be eluted as a sharppeak using BY columns. Using the Câ€”l8RD mode, four majorfractions are resolved in both EHDP and MDP systems, and twoor three minor ones. Optimum resolution is achieved usingeluting solvents (pH 7.8) containing appropriate combina





tions of dioxane, ligand, NBu4@ ion, and CH3COONa. Effect oftime, heating, and oxygen was studied for both agents. hasue distribution in mice of the major fractions showed subtbe differences in blood clearance, bone and soft tissue uptake, and excretion. Reverse phase HPLC offers unique capabilities for separating multicomponent Icâ€”99mâ€”radiopharmaceuticab mixtures and understanding their chemistry and biological behavior which is necessary for the development ofbetter and more effective agents for clinical use.

This work was supported by Interagency Agreement#224â€”79â€”3002between the FDA and the DOE.

TECHNETIUM.-99 COMPLEXES OF OXYGENAND NITROGEN DONOR LIGANDS. A.B. Packard, S.C. Srivastava, P. Richards, andY. Hung, Brookhaven National Laboratory, Upton, NY.

A main stumbling block in the development of more effiâ€”cacious Icâ€”99mbased imaging agents has been a lack of understanding of the coordination chemistry of Ic in reduced oxidation states. In an effort to increase our understandingof the chemistry of Tcâ€”99mwe have undertaken the study ofTcâ€”99complexes of ligands con.taining oxygen and nitrogendonor atoms. We report here the results of synthetic effortsinvolving the ligands ethybenediaminetetraacetic acid (EDIA)and 2,4â€”pentanedione(acac), both of which are â€œclassicâ€•ligands of coordination chemistry and also of interest innuclear medicine.

Ic complexes of aminepobycarboxylic acid bigands such asDTPA, EDTA, and HIDA have been the subjects of continuingclinical interest because of their importance as renal andhepatobiliary imaging agents. As yet, however, there existslittle direct evidence as to the precise composition of Iccomplexes of these ligands. We have recently isolated a puregreen product resulting from the reaction of EDIA and(NH4)2IcCl6 whose properties are consistent with its formulation as [Ic(OH)2(H2EDTA)].2H2O. In aqueous solution thismaterial slowly Ã§ransforms into a red species,[Ic2(O)2(EDIA)2] . Elemental analysis, infrared and uvvisible spectra, and chromatographic data have been obtainedfor both these compounds.

Of more recent interest has been the possibility of preparing lipophilic Ic complexes which would be of interest asbrain agents and labels for blood cells. To this end we haveprepared Tc(acac)3 by reaction of NHj,TcO4with acac. Theproduct has been characterized by elemental analysis and infrared spectroscopy and is readily soluble in common organicsolvents.

This work was supported by Interagency Agreement#224â€”79â€”3002between the FDA and the DOE.

IMMUNOREACTIVITYOF Tc-99m-F(ab')2 ANTIBODY FRAGMENTS.B.A. Rhodes, S.W. Burchiel,K. Breslow, R.K. Austin,K.A. Reed. Universityof New Mexico, College of Pharmacy,Albuquerque,NM.

This study was undertakento determineif Tc-99mlabeled F(ab')2 fragmentsof IgG antibodiesto hCG retam their immunoreactivityafter radiolabeling. TheFc portion of the IgG was removed by pepsin digestion.The digest was fractionatedby SephadexG-15O columnchromatographyand the F(ab')2 fractionconcentratedbynegative pressuredialysis. The proteinswere then pretinned and freeze dried to prepare kits for labelingwithTc-99m. The freeze dried kits were reconstitutedwithup to 50 mCi of Tc-99m. In some cases, human serumalbumin was added as a carrier protein,and the mixtureasepticallypassed through a small, stannous ion treatedSephadexG-25 mini column to remove non-proteinboundTc-radiochemicalimpurities. The Tc-preparationswereevaluatedfor imunoreactivity by measuring the percentageof Tc specificallybound to hCG-coupledSepharosebeads.Yields of imunoreactive Tc as high as 80% have beenobtained. Control tests were carried out with 1-125 andI-131labeledIgGand F(ab')2fragments,andwithTc-99mand iodinatednon-ininuneIgG and F(ab' @2fragmentsrunin parallel,topermit calculationof ininunospecificbinding. It is concludedthat Tc-99m-F(ab')2preparationsof high specificactivity (greaterthan 100 mCi/mg) canbe preparedwhich retain their specific imunoreactivity.

ALTERATIONS IN RED CELL TAGGING WITH SULFONAMIDES. L.R.Chervu, J.J. Castronuovo, S.S. Huq, D.M. Milstein, and M.D.Blaufox. Albert Einstein College of Medicine, Bronx, NY.

There is increasing awareness of potential alterationsin the biodistribution of radiopharmaceuticals as a resultof patient medication and therapy. Recently intense vascubar pooling of Icâ€”99mwas noted after the IV injection ofTcâ€”99mâ€”pertechnetatefor brain scanning in 3 patients (pts)who had no prior nuclear medicine procedure. All 3 pts hadreceived sulfamethoxazole and trimethoprim prior to thebrain scans. In 1 pt, 75% red blood cell (RBC) tagging wasnoted. In another pt, a repeat brain scan with Icâ€”99mâ€”DTPArevealed no excess vascular activity on delayed images.The role of the sulfonamide drugs in respect to the RBCtagging with Icâ€”99mâ€”pertechnetatewas studied in animalmodels because of these clinical observations.

Six male rats and lb male rabbits received sulfonamidesand trimethoprim individually and in combination. hcâ€”99mâ€”pertechnetate was injected after loading and images wereobtained up to 4 hours post injection after which RBC tagging was measured. Eight control rabbits and 6 rats alsowere imaged and blood samples analyzed. RBC tagging rangedfrom 37.9% to 62.4% in 4 medicated rabbits and the rest ofthe medicated group showed tagging to a lesser degree. Onecontrol rabbit showed RBC tagging of 16.9% and the rest<5%. Control and experimental rats revealed 9 to 25% RBCtagging.

Sulfonamides administered in rabbits would thus seem tovariably affect the biodistribution of Icâ€”99mâ€”pertechnetateby RBC tagging, the mechanism for which is unclear. Basedon the results with animals and the clinical observation,the possibility of RBC tagging in pta with prior sulfonamide medication should be considered.

STUDIES OF RED BLOOD CELL (RBC) LABELING: RATEOF BINDING OF Tc-99M TO HEMOGLOBIN (11gb) IN THEINTACT CELL AND Hgb SOLUTION. L,.,L,..&illah&n.1@[email protected].,@@ M&Liiiii@k@.@ Â£trauas.Massachusetts General Hospital, Boston, MA.

To aid in the elucidation of mechanisms involved inlabeling human red blood cells with Tc-99m1 we havecompared the rate of Tc-99mincorporation into intact redblood cells to the rate of incorporation of Tc-99m intohemoglobin prepared by the hemolysis of packed red bloodcells. To study Tc-99m incorporation@into red bloodcells, ten patients were pretreated with stannous ion byan intravenous injection of stannous pyrophosphate (1 mgSnCl2) twenty minutes prior to withdrawal of blood. AlOml heparinizedblood samplewas obtained and 25-lOOuCiof Tc-99m pertechnetate were added. At time intervalsfrom one to ten minutes, samplesverÃ§removed and addedto solutions of stannous DTPA (10-3M) to terminate thelabeling reaction. Red blood cells were separated bycentrifugation and labeling efficiency determined foreach time period. Iran@port of Tc-99m from plasma to redblood cells proceeded with a rate constant of 0.35 mon -1reaching a labeling efficiency of 89.5 + 6.4% at 10minutes (meanÂ±SD,nlO). To determine tEe uptake ofTc-99m by 11gb,blood samples were obtained fFomvolunteers and 2m1 packed cells were lysed with 2mldistilled water. After centrifugation (l500g), 1 ml ofhemolysatewas added to a Brookhavenred blood celllabeling kit as a source of stannous ion, Twenty-five tolOOuCi of Tc-99m pertechnetatewere then added and attime intervals from one to ten minutes sample@ werewithdrawn and added to stannous DTPA as described above.Labeled Hgb was isolated by Sephadex G-25 gel filtration.A labeling efficiency of 95.3Â±1.3% (meanÂ±SD,n12) wasobtained for all time periods, indicating the reactionbetween Tc-99m and Hgb solution was not inhibited byDTPA. These results show an association between Tc-99mand Hgb at least as strongly as between Tc-99m and DTPAand suggÃ§stthat the red blood cell membrane exerts arate limiting effect on the labeling of red blood cellswith Ic-99m.

PHYSIOLOGIC INDCATORS OF PERFUSION--CORPUSCLES LABELED ANDEMBOLIFIED. W.W. Hunter, Jr., Vanderbilt Medical Center,Nashville , Tennessee.

Ideal design criteria of radiolabeled agents for regionalperfusion scanning are essentially those properties of theblood elements whose circulation it is desired totrace.Theseinclude the absence of antigenicity and toxicity, a shortbiological halfâ€”life,and those properties influencing theflow characteristics of the blood elements such as smoothspherical shape, diameter and density. Practical considerations of clinical medicine necessitate simple and rapid labcling with shortâ€”livedradiotracers, ready availability andlow cost. Of agents proposed, newly developed PIPCLE (Physiobogic Indicators of Perfusionâ€”â€”CorpusclesLabeled and @â€”bolified) most nearly fulfills these ideal criteria. Homebogous erythrocytes are diluted in a fixative solution ofglutaradehyde to provide a rigid spherical shape. After washing an aliquot of corpuscles to remove serum proteins, the

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cells are labeled with reduced 99@Tc using less than 5Ougof stannous ions. A sterile kit provides a suspension ofPIPCLE in a physiological solution for injection in lessthan 10 mm. Unable to fold, a process which is necessaryfor passage through the pulmonary capillaries, embobifiederythrocytes constitute an extremely uniform and ideallysized agent for studies of lung perfusion. Excellent lungscans can be obtained with as few9@ 50,000 erythrocyte PIPCLES labeled with several mCi of â€œIc.Biological halftimes are between one and two hours. The homogeneous andphysiologic nature of PIPCLES should provide more definitiveinformation from clinical studies of [email protected] constituents, radiolabeled in high apecific activity, can be expected to temporarily blockade only the anallest vessels of the microcirulation,thus providing a markedimprovementin safety@ver many previously described preparations.

Tcâ€”99mL.ABELEDDEXTRANâ€” A [email protected]@M@?fI FORGAhH@RADIONU@LIIE AN@IO@AP1W. E. Henze, C. Robinson, D.E.Kuhl , H.R @Schelbert. UCLASchool of Medicine , Los Angeles , CA

ho overc@ limitations of currently employed Tcâ€”99malbunine and in vivo or in vitro labeled red blood cells forequilibrius gated @4ood pool imaging (GPI), we labeled bcâ€”99mpertechnetate by Sn reduction to dextran of different molecularweights (40,000 Dalton@TcDx 40, 5@O,OOO@rCDX5@O; 2 ,000,000.'FCDX2,000) and tested body distribution, kinetics and suitability forblood pool imaging in 7 mongrel dogs. Sn reagent dextran kitpreparations (1 ml dextran 10%) were stored for weeks and bcâ€”99mpertechnetate addnd minutes prior to injection. The labelingefficiency was in excess of 981 as shewn by paperchromatography. Icâ€”99mremainel totally bound to dextran invivo : There was no evidence for free Icâ€”99m in blood , urine,thyroid, stomach or salivary glands. Activity was excretedthrough the kidney only in the form of Tcâ€”99mdextran. Whelebody distribution shewed appreciable activity only in thecirculatory system, the liver and urinary bladder. The organactivity time course depended upon the molecular weight ofdextran used . bcDx 40 shewed a high initial urinary excretionrate while TcDx 2 ,000 was initially accueulated in the liver andthen excreted which caused a fast decline in blood activity.Blood pool activity was optimal with TcDx W with a clearancehalf time of about 2 hours. With this agent optimtsn GPI could beobtained within 1 hour, with a target to background ratio of 9.1decreasing to 7.3 within 60 minutes after injection. Thecorresponding ratios for in vitro labeled rnd blood cells asoptimtin reference were 9.9 and 9.1We conclude that Icâ€”99mdextran is a nme agent suitable for bloodpool imaging. Its advantages are simple chemical preparation andtechnical handling as wall as its extremely stable labeling.High contrast GM studies can be obtained until 1 bour afterinjection if using TcDx 5L@O.

ORNITHINE DECARBOXYLASE: A TARGET ENZYME FOR IMAGING WIThRADIOLABELED ENZYME INHIBITORS. M.C. Tobes, D.L. Gildersleeve, R.W. Thompson, N.W. Thompson, and W.H. Beierwaltes.University of Michigan, Nuclear Medicine Division, AnnArbor, MI.

Based on the view that ornithine decarboxylase (ODC) andSâ€”adenosylmethioninedecarboxylase (SAND), the rateâ€”limiting polyamine biosynthetic enzymes, may be enzyme markersfor human cancers, we have examined the potential for thedevelopment of an enzymespecific radiolabeled inhibitortoward these enzymes for nonâ€”invasivediagnosis of thyroidcarcinomas. ODC and SAND activities were measured in 27surgical specimens from normal and various pathologicalthyroids.

Both the ODC and SAND activities were elevated in folbicular, papillary, and medullary carcinomas as compared tonormal and other pathological thyroids. The increase inODC activity in these carcinomas (24 to 201 fold) is, however, greater than the increase observed for SAND activity(2.4 to 6.1 fold). Both ODC and SAND activities were alsoelevated in a metastasis of medublary carcinoma, but againthe elevation in ODC activity was significantly greater.

These results and the recently reported increase in ODCand SAND activities with malignancy in human epithebomassuggest that these enzymatic activities'may be general biochemical markers of human cancers and that the elevation ofODC activity is significantlygreater. ODC may, therefore,be a preferential target for the development of radiopharm

aceutical agents for the imaging of human cancers. Successful approaches towards imaging with ODC as the target enzyme may involve radiolabeled monocbonal antibodies to ODCor the many known inhibitors of ODC such as the suicide inactivator difluoromethybornithine which might be positronlabeled.

Sn-ll7m AS A POTENTIAL RED BLOOD CELL LABEL. J.M. Waud,U.N. Drew, T. Duelfer, H.N. Wagner, Jr., and F.F. Knapp.The Johns Hopkins Medical Institutions, Baltimore,@ andOak Ridge National Laboratory, Oak Ridge, Tenn.

We have investigated the use of Sn-117m as a red bloodcell label. Sn-ll7m (tÂ½ l3.6d. 2y, 158 keV) was reactorproduced as the metal. The Sn-ll7m was then prepared foruse as stannous chloride. The stannous chloride stock solution was assayed by periodate titration. Red blood cellsfrom normal volunteers were then incubated with varyingconcentrations of stannous chloride. The labelling efficiency was approximately 70%. A single washing removed essentially all the free Sn. Further washings failed to removeany additional label, suggesting that the label was strongly bound. Oxidized tin, presumably in the stannic form,also labeled RBCs but with a lower efficiency than thestannous ion. We also found that in the concentrationrange from approximately 10-100 ng/ml final stannic concentration, there was an inverse relation between concentration and labelling efficiency. Initial comparisons withCr-5l labelled red blood cells suggest that Sn-ll7m may bea useful agent for red cell volume studies. Sn-117m isprocedurally easier to use than pertechnetate and has amore favorable photon/rad ratio than Cr-51. Further, ifSn-ll7m of higher specific activity can be produced by highenergy spallation, this agent may be useful for gated bloodpool studies.

GOLDAu-b9@m, SHORTLIVID SIIGLE PIVItX4 EMITFERFORHEIvDDYNAMIC S'[email protected]. Garcia, I. Mena, R. DeJong and J. Fain.Division of Nuclear Medicine, L@ Harbor-UCA MedicalCenter , Thrrance , CA and Byk Mallinkrodt Petten , Holland.

Search for slxrt-lived radionclides has concerned cairfield for manyyears. A nowsuch radionuclide is Au-b9@n(T@=3O.5 see) generated fran Hg b9On (T@=4Ohrs).@tinnxnlimaging of Au-19On (261 Key) using analog gamma camerasrequires that it is relatively free of the high energy contamination of Hg-b9fsn (560 1Gev) and Hg-b95 (up to 1 . 171 rnevT@=9.5 bra). Thus, we calculated the percent contaminationfran repeated ebutions of the Hg-b9@n/Au-b9@n generator. Weimaged line spread functions by means of a constant infusion of Au-l9On using a UOV camera with a 280 Key collimator and also with a biplane bow energy collimator, (@).When we ebuted the generator 10 times in sequence endallowed a buildup of Au-l9fzn during 3 minutes before eluting with 2. 5 ml , the contamination in this eluate was lessthan 0.3% ([email protected]@) of Hg for the first tw weeks. Weobtained the following results:

At Face 4@ an ScatterColbitmator FWHM FW1O@M }WHM @Wl@Y@M280 Key 11.4 inn 20. 0 rim 13.6 mm 37.9 mmBiplane 12.1 mm 33.6 ma 17.8 mm 44.0 mmThus , with less than 0.3% high energy contamination , the230 Key collimator is effective for imaging Au-l9Emwhilethe biplane collin ator although adequate, shows signs ofseptal penetration of 261 Key photons . Radiation exposurefran An-l9.@m is as fobbcaws : Heart 0. 78 mrad/mc and kidneys0.56 mrad/me. Exposure from Hg is a function of thefractional leakage fran generator. The imaging and mdiation exposure characteristics of the 30.5 sec half lifeAu-l9ftn are pmcznising of a significant clinical contribution in the field of adult and pediatmic hamxlynamics.

FEASIBILITY STUDIES FOR THE USE OF Ba-l37m IN FIRSTâ€”PASSRADIONUCLIDE VENTRICULOGRAPHYWITH A MULTICRYSTAL GAMMACAMERA. J.L. Lazewatsky, F.P. Castronovo, and D.E. Tow.West Roxbury VA Medical Center and Massachusetts GeneralHospital, Boston, MA.

Baâ€”137mis a 2.6â€”minutehalfâ€”lifegeneratorâ€”producedradionuclide (parent, Csâ€”137,halfâ€”bife=3Oy)which hasbeen available for some years. The daughter emits a 661KeV gamma ray and yields a wholeâ€”bodyradiation dose of ap

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proximately 0.6 mRad/mCi. This compares with 10 mRad/mCifor Tcâ€”99m.We have investigated the physical performanceof the multicrystab camera (Baird System 77) with Baâ€”l37min preparation for its investigation as an agent for firstpass ventricubography. The extrinsic lineâ€”spreadfunction(LSF) yields a FWHN of 0.7 cm with and without backscattering material at the collimator face and 1.8 cm and 1.4cm at 7 cm from the collimator with and without lucite absorber (backscatter was present for both) . Some tailingis present in the LSF amounting to 22% of the maximum at 3standard deviations from the mean. These data compare with.53 cm at the collimator surface and 2.1 cm at 7.6 cm fromthe collimator for Tcâ€”99mwith the same camera. No significant tailing is present with Tcâ€”99m. For a 2 cm, 200@iCiCsâ€”137source, the sensitivity is 2150 cps/mCi. Thiscompares with 40,533 cpa/mCi for Tcâ€”99m. All Baâ€”l37mmeasurements were made with a 6.4 cmâ€”highlead collimator anda 40% energy window, while Icâ€”99mmeasurements used a 2.5cm bead collimator and a 50% energy window. These measurements yield a required Baâ€”137m dose of 50 mCi for afirstâ€”passRVG. This is a radiation dose reduction of afactor greater than 6 over Tcâ€”99m. These results combinedwith the known physical properties of Baâ€”l37msuggest thatit has promise as a convenient and versatile agent forfirstâ€”passRVG imaging.

MEDICATION INDUCED CHANGES IN BIODISTRIBUTION OF RADIOPHARMACEUTICALS . L .R. Chervu , S.S. }luq, J .A. Joseph,S.B. Chun, and M.D. Blaufox. Albert Einstein College ofMedicine, Bronx, NY.

There is increasing evidence that the biodistribution ofradiophammaceuticals in humans is influenced significantlyby drug interactions or interventions which are not properby appreciated or documented. In an effort to understandthese drug related influences, a systematic investigationof alterationin radiopharmaceuticalbiodistributioninmice administered commonly used medications including inderal, coumarin, penicillin, tapazole, propyithiouracil,lasix, aldomet, hydrochlorothiazide, lithium carbonate,phenobarbital, dilantin, digoxin and indomethacin was done.These drugs were given p.o. , i.p. â€¢or i.m. over a period of7 days at the end of which, 1 of 5 radiophammaceuticals,Tcâ€”99mpertechnetate, Snâ€”Icâ€”99mpertechnetate, Tc-99mâ€”MDP,Tcâ€”99mâ€”GILA,Tcâ€”99mâ€”HIDAwas injected in each set of animalsand the biodistribution compared with a control group 1hour post administration. Deviations in organ distribution from the control group were noted with all medications, i.e. with propyithiouracil, the % dose with Snâ€”Tc99m pertechnetate in experimental vs control animal was:blood 17.0Â±1.1vs 35.7Â±0.7; heart, 0.40Â±0.06 vs 0.54Â±0.07;kidneys, 2.2Â±0.6vs 9.8Â±0.9; liver, 1.20Â±0.01vs 6.9Â±0.2;testes, 0.24Â±0.01 vs 0.16Â±0.03; thyroid, 0.6Â±0.1vs0.30Â±0.02. These variations reflect subtle endogenousdrug interactions on the localization and clearance ofradiophammaceuticals. Altered uptake in several criticalorgans siaycause misinterpretation of the procedure andmay affect the radiation doses which these organs receivein specific studies.

CONTROVERSIAL MECHANISM OF TECHNETIUMâ€”99mDEPOSITION ONBONE. N. D. Francis, P. A. Horn and A. J. Tofe, TheProcter & Gamble Company, Miami Valley Laboratories,Cincinnati, OH.

The purpose of this research was to determine theimportance of collagen matrix vs. inorganic apatite inthe deposition of Tc99m from bone scintigraphic agents.Pure inorganic apatite (HA) and pure organic rat bonematrix (OM) were reacted with Tc99mâ€”HMDPto provide acompetitive adsorption envirorsnent for the Tc99m. After5 mm. reaction, the solids ware filtered through 0.@I5iiMillipore filter, hydrogen bonding was broken between theHA and the ON with absolute alcohol, and the two solidsseparated by CHC1, differential density and assayed forTc99m. When HA aridOH compete In the same system (as isthe case 2_@i@ the Tc99m adsorbs preferentially tothe HA (Ic99mâ€”HA/Tc99mâ€”OM: 140/1).

METABOLIC INACTIVATION DUE TO BINDING WITH TECHNETIUM-99m:DOUBLE TRACER STUDIES WITH Tc-99m AND P-32 OR As-76 LABELEDRADIOPHARMACEUTICALS. P. Hosain, F. Hosain, P.K. Sripada,

and R.P. Spencer. University of Texas Health ScienceCenter at Houston, and University of Connecticut HealthCenter at Fammington.

Technetiumâ€”99mlabeled compounds are usually unsuitablefor metabolic studies. However, this has not been scientifically documented. Studies were carried out with anabogous compounds, such as Pâ€”32labeled hydroxyethylenediphosphonate (HEDP) and pyrophosphate (PPi). These compoundswere then labeled with Tcâ€”99mand biodistribution studieswere carried out in mice. Biodistribution of Tcâ€”99mandPâ€”32was found to be distinctly different in case of PPi,but that in case of HEDP was almost identical. Althoughthe behavior of Tc-99m labeled HEDP and PPi was similar.For example: the excretion of radioactivity at 2h was lessthan 15% in case of Pâ€”32PPi compared to 50-60% for theother 3 agents. PPi is known to metabolize readily whereasHEDP does not react with any enzyme. This suggested thatPPi became a poor substrate due to complex formation witha cationic species of Icâ€”99m. Similarly, Asâ€”76labeledarsonomethyiphosphonic acid (AMPA) and arsonoacetic acid(AA.A) were synthesized and labeled with Icâ€”99m. Doubletracer biodistribution studies in mice showed an identicalbehavior of Asâ€”76and Tcâ€”99mwhen associated with AMPA (ananalog of methybenediphosphonate), but the behavior ofAsâ€”76and Tcâ€”99mwas significantly different with AAA (ananalog of phosphonoacetate). This was probably due to thefact that A.Anwas metabolically active which became mactivated due to binding with Tcâ€”99m. A Tcâ€”99mcomplex of asubstrate is likely to preclude essential cations (such asMg or Mn) sometimes necessary for enzymatic reactions, thusrendering the complex unsuitable for metabolism.

IN YI\V TRANSFORMATIONS OF TECHNETIUM-99M PYROPHOSPHATE.M.W. Billinghurst, I.D. Greenberg, J.B. Sutherland.Health Sciences Centre, Winnipeg, Man.

While technetium 99m pyrophosphate has been widely usedas a bone scanning agent for many years, very little isknown of what happens to this radiopharmaceutical onceit enters the blood stream. In an attempt to gathersome information about the in vivo fate of this radiopharmaceutical we collected blood and urine samples froma number of patients receiving routine bone scans. Oneml portions of this urine and serum were chromatographedon a gel (Bio gel P-lu) column. These chromatogramsdemonstrated that normally 2@ hours post injectionapproximately 90% of the Tc-99m in the serum is associated with the serum proteins while the remaining Tc-99min the serum is in the form of Tc-99m chelates. No peakcorresponding to Tc-99m pyrophosphate was observed. AllTc-99m chelates where observed to be doted later thanTc-99m pyrophosphate but earlier than pertechnetate.The principle Tc-99m chelate peak corresponded to thepeak observed for Tc-99m stannous phosphate while asomewhat smaller chelate was also apparent usuallyappearing in the form of a shoulder on the side of themajor chelate peaks. Corresponding analysis of the urineshowed the presence of Tc-99m pyrophosphate as well asTc-99m radioactivity corresponding to Tc-99m stannousphosphate and this unknown smaller chelate.

INSTANT SPOT TEST FOR Sn(II) IN Tc-99m RADIOPHARMACEUTICALS AND KIT REAGENTS. T. H. Lin,M. D. Garrett, A. Khentigan, D. Lum, J. F. Lamb, andH.S. Winchell. Medi-Physics, Inc., Emeryvilie, CA.

The efficacy of Tc-99m radiopharmaceuticals and theirprecursor kit reagents depends, among other factors, uponthe presence of a sufficient quantity of Sn(r[)to (a) reducepertechnetate-Tc-99m to a lower oxidation state for properchelation and (b) keep the radiopharmaceutical in areducing environment in order to avoid re-oxidation of theproduct. Kit reagents, manufactured in aqueous or lyophiized form, may be subject to sample variability and/ordilution. A simple and convenient test for Sn(II) in theseproducts was developed for use in the nuclear medical laboratory to insure product efficacy before patient administration.

Ammonium phosphornolybdate impregnated paper Isused in the test. When a drop of the sample to be tested isplaced on the white test paper, reducing agents such asSn(H) will reduce phosphomolybdate to â€œmolybdenum blue.â€•A blue spot therefore indicates the presence of Sn(Ifl. The

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Desoxyribonuclease I(Dhase)forms stable cornplexes with the contractile protein actin. Injured myocardial cells,occuring in the hypercalcemic inyocardiopathy of Walker carcinoma bearing ruts(HMR)and isoproterenol(85 mg/kg i.p.)treated rats(ITR)should expose intracellularactin and provide access to i.v. injected la â€”beled DNase. 0.5 mCi 1â€”131 DNase(ID),radiola â€”beled by the chloramineâ€”T method and tagged withfluorescamine(IDF),was injected into 3 HNR,6 ITRand 6 control rats(CR).At 0.5-6 hrs the animalswere imaged with a'j--camera.After removing thehearts and counting them in a well scintillationcounter, thin sections were prepared for histological exainination.Myocardial cell necroses recognized in hematoxylinâ€”eosin stained sectionsshowed a bright fluorescence after IDF application into HMR.Compared to CR there was 8-10times increased heart uptake(p<O.OO1)in all ITR.In contrast to CR in all ITR and HMR the heartcould be imaged with they-camera 3 hrs afterisoproterenol application.When 0.5 mCi Tcâ€”99mâ€”humanâ€”serum-albumin was injected into 2 ITR tocorrect for blood background radioactivity, thehorseshoeâ€”shaped myocardium could be delineatedwith high contrast.Thus radiobabeled DNaseappears to be a promising tracer for rapid external detection of myocardial cell injury occuring in myocardial infarct and disordersallied with myocardial cell necroses.

Br-75 OR Brâ€”77-p-BROMOSPIROPERIDOL,AN IMAGING AGENT FORDOPANINE RECEPTORS . A. M. Friedman, C . C. Huang, H.Kulmala, R. Dinerstein and B. Brunsden. University ofChicago, Chicago, IL and Argonne National Laboratory,Argonne, IL.

Imaging agents for Dopamine (DA) receptors in the central nervous system are of obvious use in studying theprogress of disease, such as Parkinson's disease orHuntington's chorea and are of potential value in studiesof schizophrenia. We have previouslyshown that pâ€”bronospiroperidol binds strongly to DA receptors in vitro withKi â€”@ We now find that it has a high specificityin vivo to DA receptors, with a striatum/cerebellum ratioof 6.8/1, and can be displaced by normal spiroperidol. Itcan be made in high specific activity with Brâ€”75in a formsuitable for positronemission tomography. In this studywe have used Brâ€”77â€”pâ€”bromospiroperidoland a seven pinholecollimator as a single photon tomograph to image DA receptore in vivo in the striatum of a cat. We have observedthe washout, concentration, and displacement of the drugover a five hour time course and have measured a striatum/cerebellum ratio greater than 4/1 with these techniques.

IN VITRO BINDING STUDIES OF NEW BUTYROPHENONE ANALOGUESDESIGNEDTO INTERACTWITH DOPAMINERECEPTORS. S. Pogun,J. Waud, H.D. Burns, E.G. Corley, T. Duelfer, B. Dranbauer,N. Kuhar,andH.N.Wagner,Jr. JohnsHopkinsMedicalInstitutions,Baltimore,MD.

To assess quantitatively the regional distribution ofdopamine receptors in the brain in vivo, it is necessary tosynthesizeappropriateligands labeledwith positronorgama emitting radionuclides. Analogueswhich containfluorine,bromine,and iodine are particularlyof interest.In the present study, in vitro binding assays were performed to study the interactionof several new butyrophenone analoguesthat we have designedand synthesized.These assays were performedusing dopamine receptorsisolated from the corpus striatumof male Sprague Dawley ratsaccordingto the procedureof I. Creese. H-3 spiperonewasused to assess competitivebinding by the new compounds.The bound fractionwas separatedfrom the free by vacuumfiltration. IC-50 values were obtained. Our results suggest that norfluoro-bromobenperldol and norfluoro-amlnobenperidolinteractweakly with dopamine receptors (IC-500.1 micromolar) while a spiperone analogue, N(p-fluorobutyrophenon-4â€˜-yl)-4-carbamide-4-(Nâ€˜-phenylamino)piperi-dine, demonstratedno measurablebinding. A secondspiperoneanalogue, l-oxo-4 (p-bromophenyl)-8-(p-fluorobutyrophenon-3'-yl)-2,4,8-triazospiro[4.5]decane, whichwas first preparedand studied by Friedmanet al, bound

response is instant and the sample size needed is minimal.With the help of a standard color chart, this test papermay also be used in instant quantitation of Sn(H) concentration.

For the last several years we have employed an in-housetesting protocol for this spot test. Tests were performedon the samples both before and after labeling with Tc-99m.The results so far indicate that this spot test is very usefulin assuring good radiopharinaceutical preparations.

â€˜I'HESTANNOUS INDICATOR SPOT TEST: A SEMI-QUANTITATIVE TESTFOR STANNOUS LEVEL DETERMINATIONS IN RADIOPHARMACEUTICALKITS. A.M. Zimmer and S.M. Spies. NorthwesternMemorial Hospital, Chicago, IL.

The purpose of this investigation was to develop asimplified, semiâ€”quantitativetest for determining stannous levels in Tcâ€”99mâ€”Snâ€”radiopharmaceutical kits. Thetest is based on the lightâ€”activated formation and disappearance of a red complex in the presence of stannous ionand an acidifiedporp&iorinsolution (4â€”Nâ€”methylpyridylporphine tosylate). The technique involves spotting thestannous solution to be tested on chromatography paper(Whatman 31ET), followed immediately by adding the porphorin solution (4 mg/mb) onto the previous spot. Thespotted paper is then placed approximately 5 cm from ahigh intensity light source (30 watt bulb), the lightsource turned on, and the time of spot disappearance recorded. The time of spot disappearance is directly proportional to the initial stannous concentration spotted.The stannous concentration corresponding to the appropriate spot disappearance time is then obtained using astandard curve. The procedure is easy to use, requiringonly a high intensity light source and a timing device.The test is also sensitive, detecting stannous levels aslom as 40 ug/ml, accurate, and reproducible. Because theprocedure is rapid, taking less than 5 minutes to perform, it can easily be incorporated into the daily routine radiopharmaceutical quality control program.

EFFECTS OF NUTRITIVE STATE AND ANESTHESIA ON HEART UPTAKEOF FATTY ACID. L.E. Brown, T.J. Mangner, D.D. Marsh, C.A.Otto, D.M. Wieland and W.H. Beierwaltes. University ofMichigan Medical Center, Ann Arbor, MI.

In light of the widespread clinical evaluation of radiolabeled fatty acids, the present study was conducted to assees the effect of anesthesia and nutritive state on myocardial uptake of Iâ€”123â€”l6â€”iodohexadecanoicacid in rats.

Iâ€”l23â€”l6â€”iodohexadecanoicacid was synthesized by interhalogen exchange of NaIâ€”l23(15â€”20mCi) with l6â€”bromohexadecanoic acid (3 mg) in refluxing MEK. The labeled compound and the carrier bromofatty acid were formulated in 5%HSA solution.

In an initial study, fasted (24 hour) and nonfasted female Sprague Dawley rats (Nâ€”S/group)were sacrificed 5 mm.after i.v. injection of 25 @iCiof 1â€”123fatty acid. Fastedanimals showed a 43% increase in radioactivity concentration in the heart ([H]).

In a second study, fasted rats were anesthetized withsodium pentobarbital (50 mg/kg, i.p.) two hours before administration of tracer. Control rats were not given anesthesia. Experimental animals showed a small increase (10%)in [H]. However, in an identical experiment using nonfasted rats, experimental animals shoved a 94% increase in[H]. It is well known that pentobarbital has a wide spectrue of metabolic and physiologic effects.

Fasted rats exhibited higher (44â€”77%)blood radioactivity concentrations ([B]) than nonfasted animals. However,[Bj in both fasted and nonfasted rats were higher when anesthetized. In contrast, hepatic radioactivity was reduced with anesthesia in the nonfasted group.

These results suggest that nutritive and metabolic factore should be carefully considered in clinical applications of radiolabeled fatty acids.

EXTERNAL DETECTION OF MYOCARDIAL CELL INJURYWITH 1-131 DNase. S.N.Reske, K.Vyska,K.Reske@@.E.Feinendegen. Nuclear Research Center JUlich,University Mainz, FRG

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stronglyas indicatedby an IC-50 of 0.95 nanomolar. Thiscompoundand other similar analoguesappear promisingforthe study of the dopaminergicneurotransmissionsystem.

A THERAPEUTIC AND DIAGNOSTIC 1-131 CAPSULE FORMULATION WITHMINIMAL VOLATILITY AND MAXIMAL BIOAVAILABILITY. T.A. Haney,P. Wedeking, N. Morcos, M.D. Loberg. Squibb Institute forMedical Research, New Brunswick, N.J.

Therapeutic and diagnostic quantities of radioiodide aremost conveniently dispensed in capsule form. The encapsulated radioiodide must be rsdiochemically pure, readilyabsorbed, nonâ€”volatile,and nonâ€”toxic. The level of volatile radioactivity emanating from the capsules is particularly significant in maintaining a safe working environmentfor nuclear medicine personnel. This work reports the developoent of two polyethylene glycol based formulationswhich satisfy all four requirements.

The capsule formulations consist of a mixture of polyethylene glycol 1540 or 4000 and sodium thiosulphate as areducing agent. Radiochemical purity and volatility weremeasured using standard techniques. The bioavailability ofthe capsules was measured relative to that of liquid 1â€”123/1â€”124.Rabbits were simultaneously administered all radionuclides, and the relative thyroidal uptake was determinedat 4 and 24 hours.

Therapeutic capsules (25 mCi) and diagnostic capsules(50 pCi) were stored at room temperature for 72 days.Radiochemical purity values consistently exceeded 98%; relative bioavailability at 4 and 24 hours ranged between 97%and 124% of the 1â€”123/1â€”124.The volatile 1â€”131never cxceeded 10 nCi and was typically less than 1 nCi. The levelof volatile radioactivity was reduced an additional threeorders of magnitude by scavenging the container atmospherewith activated charcoal. No toxic reactions were observedin acute toxicity studies. The new capsule formulationsare efficacious and contribute to the maintenance of asafe working environment.

SEPARATION OF RACEMIC TRYPTOPHAN. J.H.C. Wu, P.V. Harper,and K.A. Lathrop. The University of Chicago, Chicago, IL.

It would appear desirable to use C-ll carboxyl L-tryptophan for pancreatic imaging rather than the racemicmixture available from the current synthetic methods. Thisshould give better localization, lower radiation absorbeddose, and possibly reduce the interference from renallocalization. Enzymatic destruction of the Dâ€”isomerrequires introduction of foreign protein into the system. Byusing the selective affinity between serum albumin and Ltryptophan, a good separation, resulting in a preparationsuitable for administration to humans, has been accomplished in our laboratories within a time consistent withthe 20â€”minutephysical half-life of Câ€”lb.Using humanserum albumin (HSA), an albumin-sgccinoylazninoethylmepharose resin was prepared which quantitatively retainsL-tryptophan but rejects D-tryptophan. Preparation ofthe resin consists of adding cyanogen bromide andsepharose-4B, coupling with ethylene diamine, and addingsuccinic anhydride, NSA, and l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. The tryptophanfraction, separated by HPLC from the reaction mixture, isadjusted to pH 9.5 and added to a column of the preparedsepharose resin and washed with borate buffer (pH 9.5)until D-tryptophan is washed off. Changing to an acetatewater ebuant (pH 3.5) removes the L-tryptophan in about6 ml when pH 5 is reached. At a flow rate of 2 ml/min.,the time for separation and elution of L-tryptophan isabout 30 minutes. The acetate concentrationis .01 M, sothat the solution, after membrane filtration, is suitablefor intravenous injection in humans.

RESOLUTION OF C-ll-DL-VALINE BY HIGH-PERFORMANCE LIQUIDCHROMATOGRAPHY. L. C. Washburn, T. T. Sun, B. L. Byrd, andA. P. Callahan*. Oak Ridge Associated Universities (ORAU)and Oak Ridge National Laboratory (ORNL) , Oak Ridge, TN.

Our modified Btichererâ€”Streckersynthesisfor Câ€”llâ€”carboxylâ€”labeledamino acids gives racemic mixtures of thoseamino acids having asymmetric centers. For physiologicalstudies, however, optically active Câ€”lbâ€”labeledamino acids

are required. We have developed a highâ€”performanceliquidchroinatographic (HPLC) method for resolution of Câ€”llâ€”DLvaline. A conventional reverse phase preparative UPLC coburns (Ultrasphere ODS, 5 @i,10 me x 25 cm) and a chiralmobile phase (0.017 M Lâ€”probineand 0.008 M cupric acetatein 0.03 M sodium acetate) were used, The Biichererâ€”Streckertechniquewas furthermodified to reduce the volume of thereaction mixture to 1.5 ml. Following neutralization with500 iii.of concentrated HC1, 3.2 mg of cupric acetate and3.9 mg of Lâ€”prolinewere added, and the mixture was microfiltered and loaded onto the column. Ebution patterns warefollowed using a liquid column single channel analyzermonitor, by fraction collection followed by liquid scintillation counting when a Câ€”l4tracer was used, or by use ofa refractive index detector when pure DLâ€”,Dâ€”,and Lâ€”valinewere used. At a flow rate of 7.2 mb/mm, the entire separation required 12 sin. Copper can be removed from the Lâ€”amino acid fraction by precipitation with hydrogen sulfide,and final purification by cationâ€”exchangechromatographygives Câ€”llâ€”Lâ€”valinein a form which should be acceptablefor clinicaluse. We are presentlyattemptingto adapt theprocedure to resolution of other Câ€”lbâ€”labeledamino acids.(Work supported by contract number DEâ€”ACO5â€”760R00033between the U. S. Department of Energy (DOE) and ORAU; ORNLis operated by Union Carbide Corp. under contract Wâ€”7405â€”engâ€”26with the U. S. DOE.'l

A RAPID METHODOF RADIOCHEMICAL PURITY FOR Tc-99m RADIOPHARMACEUTICALS.Y.I.C. Cohen and M.R. Besnard.Pharmacology ERA-CNRS 627. Univ.Paris XI. Chatenayâ€”Malabry.F 92290

Several methods have been developped to evaluate theradiochemical purity of Tcâ€”99mradiopharmaceuticals. Aright estimation of this purity ask for two different separation of the Tc radiopharmaceutical from its two majorimpurities,i.e.pertechnetate and colloidal technetium.Thisdouble procedure is needed by the fact that reduced technetiuni is easily oxidized by molecular oxygen.We have cxtended to several Tc compounds a chromatographic systemproposed for Tcâ€”pyrophosphate(PYP).On a ITLCâ€”SGchromatographic plate (GELMAN),methylâ€”ethylâ€”ketonis allowed torun,about 8 min,in a first step,followed by a molar sodiumacetate solution run of 10 min,in a second step. Betweenthe two runs,the plate is air dried during 5 mm. 0.005 mlof Tc radiopharmaceutical solution is previously applied.During the first run,17 cm long,pertechnetate (Rf 1) is separated from other Tc compounds of lower valence state(RI O).During the second run,8cm long,Tc radiopharmaceutical moves with sodium acetate solution front while colloidal Tc remains at the start line.Thus on the same plate wehave,from the start line to the top,in order,colloidaltechnetium,Tc radiopharmaceutical and pertechnetate.The duration of whole analysis is of 30 mm including the counting of the plate.With this chromatographic system,we haveanalyzed Tc PYP,Tc DTPA,Tc gluconate. The radiochemical purity is found between 94.1 and 97.8 % for the three compounds;colloidal impurity ranges from 0.4 to 0.8 Z,pertechnetate accounts for 0.4 to 2.6 %.A diffuse radicactivityalong the trail amounts to 0.6 to 4.7 %. This fast and reproducible chromatographic system allows a rapid check ofTcâ€”99mradiopharmaceuticals before injection to the patient

SYNTHESISOF N-l3 LABELED MONOCARBOXYLICAMINO ACIDS,SUITABLE FOR PATIENT STUDIES,WITH If'tIOBILIZEDGLUTAMATEDEHYDROGENASE. A.S. Gelbard,A.J.L. Cooper, R.E. Relman,andR.S.Benua.MemorialSloan-KetteringCancerCenterand Cornell UniversityMedical College, New York, NY.

We havemodifiedourmethodforlabelingN-l3-L-glutamate with glutamatedehydrogenaseImobilized onto CNBractivatedSepharose(A.S.Gelbardet al.,J. Mud. Med.21:988-991,1980)in sucha manneras to producehigh@Teldsof pyrogen-free, radlopure (>99.7%) N-13-L-monocarboxylicaminoacids. Thesemodificationsinclude:(1)increasingthe volume of the Sepharosesupport to equalthe volume of the reactionmixture; (2) raising the pH ofthereactionmixtureto 9.0;(3)increasingtheconcentration of the a-keto acid to 25 mM; and (4) incubatingthe reactionmixture with the bound enzyme on the Sepharose column for 10 mInutes. To date we have labeled thefollowingaminoacidswithN-l3:L-valine,L-methionlne,L-leucine,L-alanineand L-cs-amlnobutyrate.The radiochemicalyields have ranged from 16-60% and the radio

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activity in the final product varied from 5-28 mCiwiththe higher yields obtained in the preparationof labeledvaline,methionineandci-aminobutyrate.

Comparative whole body images of human volunteersusingNâ€”l3â€”L-glutamateandNâ€”13â€”Lâ€”valineindicatethatN-l3derivedfromvalinelocalizesto a higherdegreeinthe pancreasbut to a lower degree in the liver. In contrastto N-13-L-glutamate,thereisminimaluptakeoflabelIn themyocardiumafterI.V.injectionof N-l3-L-valine.

The presentwork extends the number of N-13-L-aminoacidsthatareavailableforclinicalstudiesto includeessentialbranchedchain-andS-containingaminoacids.

MYOCARDIALUPTAKE OF lO-[â€•C]-9-TELLURAHEPTADECANOICACID(lO-[1@C]-9-THDA): EVIDENCEFOR RETENTIONOF THE ALKYLREGION OF 9-THDA. F F Knapp Jr. M Vest *D RElmaleh â€˜@RH Liss *H W Strauss 1 A Ferren andA P Callahan.NuclearMedicineTech.Group,OakRidgeNationalLaboratory(ORNL),OakRidge,TN,*Mass.Gen.Hosp., Boston, MA, and **ArthurD. Little, Boston, MA.

The highuptakeandprolongedmyocardlalretentionof 9-E1237'@Te)-9-THDA(I) suggeststrapping of the Intact 9-THDAmoleculeor a metabolite.Retentionof fattyacidscontaming stableTe andradiohalogenatedInthealkylregionmay representa new approachto assess myocardialmetabolism. To determinethe degree of retentionof thealkyl region, lO@[lkC]_9@ThDA(II) was tested in rats.Methyl-lO-[@C]-9-THDA was preparedby the coupling ofNa-1-['@C]-octyltellurolwithmethyl-8-bromooctanoate.The acid lO-[' C]-9-THDAwas prepared by basic hydrolysisof the purified ester. @nehr after 1@j@ctionin rats,myocardlal retentionof @Ã§from io-[ CJ-9-THDAwas verysimilar to retentionof 12 â€œicfrom 9['2l@@Tre]_9@THDA.

Rangeof 4 rats-S dose/gm Mean â€˜-HeartAgent Heart (H) Blood (B) H:Bâ€”Tn.â€”[email protected]@@(II) 4.01-5.83 0.31â€”0.5511.2 .Llver

Autoradiographicstudiesof sagittalratcarcassslicesafterInjectionof lO-[@C]-9-THDAconfirmedthespecificandpronouncedmyocardialuptakeof radioactivity.Thesecombined results Indicatethat the alkyl region of 9-THDAIs an attractiveregionfor introductionof radiohalogens.

ORNL Is operatedby Union Carbide Corporationundercontract W-7405-eng-26with the U.S. Departmentof Energy.

TA-178 AS AN IMAGINGAGENT FOR ANGER AND MULTICRYSTALCAMERAS.A.D. LeBlanc, J.L. Lacy, P.C. Johnson, L.Poliner,and S. Jhingran. Baylor College of Medicineand Johnson Space Center, NASA, Houston,TX.

Thepurposeof thisstudywas to extendpreviousworkwith Ta-178 with particular attention to the requirementsfor cardiovascularstudies.

IrradiatedTantalum foils were dissolvedand purifiedusing publishedtechniquesto obtain Tungsten-178. AWâ€”l78+Ta-l78generatorwas constructedand tested. WeInvestigateddifferentcollimatorson both a multicrystalandan Angercameraby comparingTa-178andTc-99mimagesand calculatedejection fractionsobtained using a cardiacphantom.Inaddition,pulseheightspectrawereobtainedwith and without collimatorsto investigateseptal penetration. Scatter and septal penetrationof lowandmediumenergyAngercameracollimatorswereevaluatedby imagingpoint sources of Ta-178, Am-241 and Tc-99m. ItIs concludedthatTa-178canbe usedforfirstpassstudles with the multicrystal camerataking advantageof thehigh count rate capabilityof this device. The 1â€•highsensitivitycollimatorreducesseptalpenetrationtoacceptablelevels. The Tc-99m and Ta-178 processed Imageswere judged to be very close in quality. ImagingTa-178with an Anger camera and a medium energy collimatorreduced septal penetrationto acceptablelevels, but produced poorer images compared to those using Tc-99m and ahigh resolutioncollimatorbecause of poorer Inherentandcollimatorresolutionand because a greater fractionofcompton scatteredphotonsare accepted by the pulse heightanalyzer.However,forcalculatingejectionfractionsanddisplayingwallmotion,Ta-178anda mediumenergycollimatorgave satisfactoryresults.

Co-55-DTPA : A NEW POSITRON EMITTER R.ADIOPHARMACEUTICALFOR QUANTITATIVE CISTERNOGRAPHY. B. Maziare, J.M. Verret,0. Stulzaft and A. Syrota. Service Hospitalier F. Joliot â€”Depart. of Biology â€”C.E.A. ORSAY â€”FRANCE.

DTPA labeled with a convenient halfâ€”lifepositron emitter was evaluated for quantitation of cerebrospinal fluidkinetics in different areas of the brain. Coâ€”55and Cuâ€”64have, both, favorable physical properties (decay by 8+, T1/2 : 17.5 and 12.8 h respectively). They were prepared bybombardment of a natural nickel target by protons and separated by chromatography of the halogenated derivatives onan anionic resin after electrolytic dissolution of the matrix. Specific activities obtained were about 5 mCi/pg forboth isotopes.Coâ€”55was then chosen in this study for itshigher production yield and its larger 8+ emission (81 % vs19 % for Cuâ€”64)although the radiation dose calculated foridentical @+activities is 1.3 higher for Coâ€”55than forCuâ€”64.A preliminarystudy showed that the others â€˜y'raysemitted by Coâ€”55did not impair the quality of the tomographic image obtained. Coâ€”55â€”DTPAwas prepared by dissolvingthis â€œnocarrier addedâ€•isotope in 0.05 N ECI, adding 100hg of DTPA and adjusting the pH to 6.6 with phosphate buffer. This chelate was tested to determine the radiochemicalpurity and the yield by chromatography using a Bioâ€”Rex70columa ; over 99 1 of the activity was bound to DTPA. Afteraddition of I ml of saline, the solution (2.5 ml) was allliporized and pyrogen tested. After a negative limulus test,1.5 n@i of the radiopharmaceutical was intrathecally administred. Tracer radioactive concentration was measured withan ECAT camara, Good quality images and quantitativedatawith acceptable statistical accuracy may be obtained duringthe first 36 hours. Coâ€”55â€”DTPAis now used to study machanisms of periventricular resorption in patients with normalpressure hydrocephalus.

COMPARISON OF GAâ€”68EDTA, C-li ciâ€”AMINOISOBUTYRICACID, ANDTC-99m PERTEGHNETATE FOR DIAGNOSIS OF BLOOD-BRAIN HARRIERDISRUPTION. L. C. Washburn, L. Dees, B. L. Byrd, T. T.Sun, and R. L. Hayes. Medical and Health Sciences Divimion, Oak Ridge Associated Universities, Oak Ridge, TN.

We used an experimental brain lesion to compare Gaâ€”68EDTA, Câ€”liczâ€”aniinoisobutyricacid (AIBA), and Tcâ€”99mpertechnetate as agents for diagnosis of bloodâ€”brain barrier(BBB) disruption. Hyperosmolar mannitol was infused intothe left internalcarotid artery of rats to induce unilateral opening of the BBB. Evans blue, injected via thetail vein 5 sin before mannitol infusion, served as avisual indicator of BBB breakdown. Gaâ€”68EDTA, Câ€”l4AIBA,or Tcâ€”99mpertechnetate was administered 1 mm after themannitol infusion. The concentration ratio of the lefthemisphere (UI) of the brain to the brain of control animals (C) is a measure of the ability to distinguish a BBBlesion in a background of normal brain. At 10 mm afterinjection, UI/C was 7.7 for Gaâ€”68EDTA, 6.0 for Câ€”l4AIBA,and 3.0 for Tcâ€”99mpertechnetate. At 30 mm, Ui/C was 24.5for Gaâ€”68EDTA, 3.4 for Câ€”l4AIM, and 3.2 for Tcâ€”99mpertechnetate. We concludethat Gaâ€”68EDTA is the superioragent of those studied, especially at 30 sin postinjection.In addition, Gaâ€”68EDTA, unlike the cosm@nly used Tcâ€”99mpertechnetate, can be used in conjunction with positrontomography, which may permit earlier and better assessmentof disease processes such as cerebral hemorrhage, braintumor, and traumatic brain injury. (This article is basedon work supported by contract number DEâ€”ACO5â€”76OR00033between the U. S. Department of Energy and Oak RidgeAssociated Universities.)

RECEPTOR BINDING RADIOTRACERS IN THE PANCREAS. DISTRIBUTION OF TRITIUM LABELED QNB, CARAZOLOL, AND PRAZOSIN. R.E.Gibson, W.C. Eckeiman, R. Fremeau, R. Patt, and R.C. Reba,George Washington University Medical Center, Washington, DC

The pancreas is known to have cholinergic innervationwhich would allow for the localization of a potent muscarinic acetylcholine receptor (mâ€”AChR)antagonist by virtue ofits interaction with the mâ€”AChR. To test whether the concentration of mâ€”AChRis sufficient to permit high pancreasto plasma ratios, the localization of JHâ€”quinuclidinyibenzilate (3Hâ€”QNB)was determined in rabbit and rat. At 2hours, 3Hâ€”QNBlocalized in the pancreas to the extent of1.85% dose/g tissue in rat (pancreas to plasma ratio of 10)and 0.35% dose/g tissue in rabbit (ratio of 9.8). Prein

Volume 22. Number 6 P75




jection of 1 mg/Kg of atropine reduced by 70% the bocalization in rabbit pancreas indicating specific binding to themâ€”AChR. The pancreas to plasma ratio was reduced to 3.2.The pancreas to liver ratio was found to be 4 for rat butonly 1.5 in rabbit. Quaternization of QNB to Nâ€”methylQNBiodide did not significantly alter the distribution oftritium.

Althougl. there is no report of adrenergic innervation ofthe pancreas, 3Hâ€”carazolol,a potent betaâ€”adrenergicantagonist, provided 0.71% dose/g tissue in the rabbit pancreas(pancreas to plasma ratio of 5.3) which was reduced by 49%upon preâ€”mnjectionof 1 mg/Kg propranobol (ratio of 2.6).The alphaâ€”adrenergicantagonist, @Hâ€”prazosin,provided 0.5%dose/g tissue in the rabbit pancreas but was not displacedby preâ€”injectionof 0.5 mg/Kg phentolammne. Since thecurrent methods of imaging pancreas depend upon aminoâ€”acidmetabolism which varies considerably among species, use ofa gammaâ€”emitting analog of QNB should provide a more reliable method for the external imaging of pancreas as theresult of its specific interaction with the mâ€”AChR.

DEVELOPMENTOF A STRONTIUM 82-RuBIDIUM GENERATOR FOB CLINTCAL APPLICATIONS . S .Vallabhaj osula ,S.Cochavi ,S.J .Goldsmith,H.Lipszyc,and H.O'Brien,Jr. Mt. Sinai Med. Ctr., N.Y.,NYand Los Alamos National Laboratory , NM.

There is increasing interest in a G2Sr..G2Rb generatorfor myocardial imaging.Performance of several column(Col)designs has been reported using bov(lâ€”lOnCi)ormoderate(25â€”5OmCi)boadsof Sr. Since the efficiency(Ef)of Cob varles with eluant ionic Â§trength,it is necessary t@ use asmuch as lOOâ€”l5Omciof O2Sr to obtain sutficient O2Rb Wehave compared several Cob designs to meet clinical and radiation safety requirements.

A 3mb Biorex Cob performed veil with 2%NaCl at pH 8.5,o.8Efandioâ€”8/miSr breakthru(BT),butthisColcannotbeused with Nb saiine,and degrades with time.Two Col obtainedfrom a coimnercial source,eiuted with O.9%NaCl had O.(Ef'andl07/mi BT but BT increasesbâ€”bOX at higher flow rates(3Omb/min)required for imaging studies.

The E@ of a 3. 5mb Alumina Col was 0.8 with 2%NaCl,decreasing to 0.6 with O.9%NaCl(2Oml)and is pH independent.Alteration of eluant ionic strength did not influence Sr BT(l07/mi).This could be reduced further to l09 to lOlO/miby the addition of a small Chelex Cob in series with a further reduction of Ef to O.14(with 2%)and O.b5(vith O.9%NaCl).BT was unaltered at flow rates l2-32mi@min.

After mCi pilot atudiea,l2OmCi of O2Sr was loaded on a3.5m1 Alumina Col.A steel jacketed depleted Uranium wellwas used as a primary shield,supplemented by Pb bricks.Atthe surface,radiation flux is O.5rnrads/hr.A millipore f11-ter at the outlet did not absorb Sr or Rb.Col performancehas been similar to the pilot yielding l5-25mCi 825b,suffi_dent for imaging,and stable>6weeks,and>3L. eluted to date.

An Alumina Cob with a Chelex trap combinesthe featuresnecessary for a clinically useful 84@b source.

NEW 82Sr/82Rb GENERATORS BASED ON INORGANIC ADSORBENTS.R.D. Neirinckx, M.D. Loberg. Squibb Institute for MedicalResearch, New Brunswick, N.J.

New generator systems for Rbâ€”82that combine the radiolytic stability of the inorganic adsorbents with low Srbreakthrough values and high Rbâ€”82yields have been dcveloped in our laboratories and are presently being evaluated for in vivo use. Because of the pyrogenicity andradiolytic instability of organic adsorbents only inorganic adsorbents were considered as supports for the generator. Hydrated SnO@,,hydrated ZrO.,,basic Ai,O3, polyantimonic acid, hydrated T1O2, TiO,fi20 and hyaratedFe203 were evaluated. Distributiofi coetficients (Ku) weremeasured for Sr(II) and Rb(I) by batch equilibrationas afunction of eluent pH and composition and duration of equilibration. Bolus size and Rbâ€”82were measured from experimental generators. Strontium breakthrough per ml of eluatewas determined as a function of eluent composition and pH,elution speed, total eluate volume and adsorbent bed size.The influence of various loading parameters on the generator's behaviour was also evaluated. Sn02 was the preferredsupport material as shown below.

Bolua Rbâ€”82 Srâ€”82Size Yield Breakthrough

__________ _______ (ml) (1) (fraction/al)

20 70 5.l(@20 90 1010 10 5.lO620 56 â€”20 60 5.108

10 70 5.l0@

PHYSIOLOGICAL CHARACTERIZATION OF A (Fâ€”18) 2-FLUORO-2â€”DEOXY-D-GLUCOSE IMPURITY. J.C. Goble, R.G. Manning,R.M. Flynn, R.M. Kessler, National Institutes of Health,Bethesda, MD

An uncharacterizedimpurityproduced as a byâ€”productof the (Fâ€”18)2â€”fluoroâ€”2â€”deoxyâ€”Dâ€”glucose(FDG) synthesishas been identified [i]. In vivo, the impurity exhibitsdecreased tissue uptake and increased plasma clearancerate compared to purified FDG. This altered physiologicalbehavior and the variable radiochemical yield (1â€”50%)makeseparation of the impurity essential in obtaining accuratevalues of local cerebral glucose metabolic rate (LCGMR).

FDG was synthesized by the method of Ido and colleagues. An additional purification step consisting ofcolumn chromatography using silica gel and an acetonitrile:water (99:1) eluant Li) was used to separate the impurity.By discarding intermediate fractions, radiochemicalseparations of greater than 98% were obtained.

Biodistribution studies performed in rabbits indicatesignificantly different physiological behavior of FDG andthe impurity. Differences in brain (p <.01), liver(p <.02) and heart (p <.02) were especially striking.Plasma clearance, evaluated in dogs using blood and urinesampling, confirmed that the impurity is cleared rapidlyfrom the blood and excreted. Differences in integralplasma concentrations were highly significant (p <.001).

Synthesis of FDG under varying conditions indicatesthat yield of the impurity is sensitive to scavenger F2concentrations in the target gas. Lower concentrationsof F2 reduce impurity yield but may compromise total Fâ€”18recovery.

[1] Personalcommunication,J. Fowler

c-Il LABELED MELANIN PRECURSORS AS RAOIOPHARMACEUTICALSFOR THE DETECTION OF EYE MELANOMA. A. van Langevelde,H.O. Beerling-van der Molen, J.G. Journde-de Korver, A.M.J.Paans, and W. Vaalburg. Dept. Nuclear Medicine, Groningenand Dept. Pharmacology, Leiden, The Netherlands.

In order to develop a radiopharmaceutical for the detection of eye melanoma the biodistribution of C-14 labeled Ltyrosine and L-3,4-dihydroxyphenylalanine (L-DOPA) was investigated in Syrian Golden hamsters with Greene melanoma.

According to the Raper-Mason scheme, melanin synthesisstarts with L-tyrosine, which is converted into L-DOPA.L-DOPA is converted into dopaquinone which, after severalsteps, polymerizes to melanin. L-DOPA is also convertedthrough dopamine into epinephrine, which accumulates inthe adrenals.

One hour after intravenous injection both L-tyrosine andDOPA, C-14 labeled, showed a high accumulation in themelanoma, higher than in eye, brain, bone or blood. Theuptake of L-OOPA in the tumor was 0.60@ 0.08 % of injectedactivity! g tissue with a tumor to blood ratio of 5.8 +0.9.For C-14 labeled tyrosine these figures were 2.22 1@ 0.38and 5.67 1 â€¢@1.43 respectively. Only in liver, kidney,adrenals and urine a higher uptake was found than in tumor.The decarboxylase inhibitor benserazide augmented theaccumulation of radioactivity in the tumor, but did notimprove the tumor to non-tumorratios. The accumulationofDL-(1-C-11) DOPA in melanoma was proved by injection ofthis compound in hamsters with a melanoma transplanted ineye or side-skin. Tomographic images of the tumor were obtamed with a positroncamera 40-80 minutes after injection.

From these data we concluded that both compounds, whenlabeledwith C-Il, are promisingradiopharmaceuticalsforthe detection of ocular melanoma.

Adsorbent Eluent@

Bioâ€”Rex70Chelex 70Al 03Zr@2Basic Al203

SnO2

NaC1 2% 8â€”9NaC1 2% 8â€”9NaCl 2% 8â€”9NaCl 0.9% 7.5NaCl 0.9% 8â€”9+l,nMP0NaCl O'@9% 7

P76 TIlE JOURNAl. 01: NUCI.I@ARMII)ICINE




ENZ'iMATICSYNTHESIS OF Nâ€”13,Câ€”llLa@LED AMINO ACIDS AND RELAT@TRICARBOXYLIC ACID CYcLE INTERMFDIATES. J .R. Barrio, J .E.Egbert, F.J. Baumgartner, E. Henze, H.R. Schelbert, M.E. Phelpsaed D.E. Kuhi. UCLA School of Medicine, Los Angeles, CA.

Sterile, pyrogen free Nâ€”b3labeled glutamate,alanine,nu glutamine, as@mrtate, and Câ€”lllabeled aspartate, oxaboacetate,citrate and malate have been produced by inmobilizing theappropriate enzymes on a c@@Brâ€”activated aephsrose support. Thesyntheses are completed 6â€”b5 minutes after cyclotron prod@tionof Nâ€”l3anaemiaor Câ€”lbcarbon dioxide. Theenzynecolumnsarereisable for several monthe witheut significant loss of enzymaticactivity. The products are free of enzyme arsf the choice ofbuffer arsi substrate concentratione are based upon suitabilityfor htmmn use. Multiple rune per day are routinely carriad outusi@ our remote semiâ€”automatic system which ensures reducedradiation exposure to the chemist to < 0.5 mR/run. Rapidverification of amino acid purity is routinely achieved byadapting the methed of oâ€”phthaldialdehyde (OPT) precolumnfluorescence derivatization. The strongly fluorescent aminoacidâ€”Oflcomplex (isoindigo derivative,A cxc 340rm; Acm 45@m@)can be separated with reversedâ€”phase HPLC arci detected tosubpicomobe levels. (Ultrasphere ODS, 5@i,4.6xl5Jiasi.d., 5@loQiat phesphatebuffer, pH 7.4 aixi 4@ M@H;flow rate, 1.0mb/mm; fluorescence and radioactivity detectors) . Theradiochanical purity of Câ€”lb labeled oxaboacetate, citrate ai@malate is determined by using a similar reversedâ€”phased HPLCsystem coupled to a radioactivity detector, but in this caseelution is done under acidic conditions. (Solvent, 98% l@1ptosphate buffer, pH 2. 5 sod 2% M@R). The radiochemicalpurities (>9 S%) aed yields ( 5 to 50 i@i) of these Câ€”ll and Nâ€”l3labeled compounds permit quantitative physiologic toomgrapby aix!kinetic analysis after intracoronary bolus injection in dogs.

I 1â€”Câ€”MUSCARINICANTAGONIST (MQNB) VISUALIZES HEART â€œINVIVOâ€•BY POSITRON EMISSION TOMOGRAPHY. M. MaziÃ¨re,C. Cepeda, G. Berger, J.M. Godot, B. Guibert, J. Sastre,M. Crouzel, R. Naquet, D. Comar.Service Hospitalier F. Joliot 91406 ORSAY â€”FRANCE.

Muscarinic cholinergic receptors are present in veryhigh concentration in the myocardium. R. Gibson (J NuclMed 20, 865, 1979) showed the specific binding of MQNB (Methiodide Quinuclidinyl Benzylate) for these receptors inthe hearts of small animals. In order to study myocardiumâ€œinvivoâ€•we have labelled MQNB which Câ€”Il,an externallydetectable radioisotope injectable to man, with which thisdrug can be isotopically labelled with a specific activityhigh enough to avoid, as much as possible, non specificbinding. I.R@NBwas labelled semiâ€”automatically,with highyield. Chemical and radiochemical purification were performed by H.P.L.C. Usually 100 mCi of 11â€”CNQNB ready for injection are obtained (30 mm EOB) with a specific activityreaching 2,3 Ci/pmole. So, the injected mass correspondingto 10 mCi required for an experiment with PET is less than10 nmoles. Cardiac kinetics were studied in curarized liwing baboon, after administration of 10 mCi. Radioactivityin blood samples was measured during the experiment. lisaging of the cardiac blood pool was performed after I.V. injection of 68CA Cl3. Results show that, for low amounts injected, NQNB is taken up rapidly by the heart and its concentration remains almost constant during the experiment.No detectable radioactivity was found in the lungs. Bloodradioactivities were very low. (Heart/blood ratio>3O, 10mmafter injection). In view of its purity, high specific activity, low toxicity, high affinity for myocardium, lowconcentration in blood abc!lungs, 11â€”CW@NB is an attractive radiopharmaceutical for myocardium studies, in man.

SYNTHESIS AND DISTRIBUTION OF Câ€”llLâ€”GLUTAMICACID (ciANDY CARBOXYL LABELED) : COMPARISON TO N-b3 Lâ€”GLUTANICACID.M.B. Cohen, L. Spolter, C.C. Chang, N.S. MacDonald andJ. Cook. V.A. Medical Center, Sepulveda, CA and UCLA.

The distribution of Câ€”lbDLâ€”alanine(P.V. Harper) is reported to be different from that of Nâ€”b3Lâ€”alanine. Methods using 5 or 6 enzymes were devised to synthesize Câ€”llLâ€”glutamic acid (GA), labeled on either the alpha or gamescarboxyl group, to compare its distribution in animals withthat of Nâ€”l3Lâ€”glutamicacid. Câ€”lbCO2 is successively converted to Câ€”lboxaboacetate, citric acid, cisâ€”aconitate,isoâ€”citrate,ciâ€”ketoglutarateand Lâ€”glutamicacid labeled onthe alpha carboxyb group. The ganmiacarboxyl group is labebed by successively converting Câ€”lbCO2 to acetate, acetyl

phosphate, acetyl CoA, citric acid, cisâ€”aconitate,isocitrate, ciâ€”ketoglutarateand Lâ€”glutamicacid. Both procedures may be halted at the next to last step to yield Câ€”ilciâ€”ketoglutaratelabeled on the alpha or gamea carboxylgroup. Alpha and gamma labeled Câ€”lbLâ€”gbutamicacid (AGAand GGA) were each administered to rabbits via ear vein.The animalswere sacrificed5 minutes later and multipletissues were obtained for sample counting. The resultswere compared to those of Nâ€”l3Lâ€”glutamicacid.

Labeling in the alpha position requires 16â€”18minutes,and 30â€”35minutes for labeling in the gamea position. Bothpathways produce yields of 12â€”20%.AGA localized poorly inthe pancreas and other organs, as compared to Nâ€”b3GA. Theresults also show that AGA was rapidly decarboxylated withloss of the Câ€”lblabel, and that GGA was also decarboxybated, but to a lesser degree. Thus, the label may not reflect the distributdonof the remainderof the originalcompound. The results also demonstrate that positronlabeled pharmaceuticals may be rapidly synthesized viacomplex enzymatic pathways.

EDTAâ€”AND DTPAâ€”COUPLEDANALOGUES LABELED WITh Tcâ€”99m.D.J. Hnatowich, D. Lanteigne, P.W. Doherty, M. Novak,B. Friedman and J. Foster. University of MassachusettsMedical School and Clark University, Worcester, MA.

We have developed a simple method of coupling ethylenediaminetetraacetic acid (EDTA) and diethybenetriaminepentaacetic acid (DTPA) groups to any primary or secondaryamine via an amide linkage. Preparation is by mixing theanhydrides of the acids with the desired amine in chboroform or in pH 7 water. As a test of this method, we havesynthesized ten straightâ€”chainhydrocarbons of chainlength C6â€”C18coupled to both EDTA and DTPA. Methods oflabeling these compounds with Tcâ€”99mwere developed andthe radiochemical purity was established by paper chromatography in two solvent systems. Biodistributions innormal mice were obtained at 30 mm and 2 hrs. Forexample, for the DTPA analogues, liver activity at 30 mmincreases linearly with increasing chain length, heartshows maximum accumulation (1.8%/gm) at C12â€”C18andmaximum heart/blood ratio (0.25) at C18. Consideringthe likelihood of different molecular charges, biodistributions for the EDTA analogues were found to be remarkably similar to the DTPA analogues of the same chainlength. Finally, the C18 DTPA analogue shows differentbiodistributions when labeled with Gaâ€”67rather than Tc99m as expected. The systematictrends with chain lengthwhich were obtained, testifies to the in vivo stabilityof both the amide bond and the corresponding chebates.This synthesis method will have applications to thecoupling of these and other similar chelating groups tomany compounds with a variety of structures of interestas potential radiopharmaceuticals.

TECNMETIUM-99m DPD - A NEW SKELETAL IMAGING AGENT.A. Schwarz, and G. Kloss. Radiochemical LaboratoryHoechst AG, Frankfurt/MAin, Federal Republic ofGermany.

Many attempts were made to improve bone affinity andstability characteristics of Technetiumâ€”boneâ€”seekingagents by chemical substitution of one or both hydrogenatoms of the methylene group of MDP. We have studiedthe relationshipsbetween chemicalstructureandskeletal uptake of phosphonic acids in which carboxygroups were introduced. Among these substances we havefound the 2.3â€”dicarboxypropaneâ€”1.1â€”diphosphonicacid(DPD), which has several advantages compared with MDP:Tcâ€”99mâ€”DPDhas a superior complex stability dependingon the presenceof two carboxygroupsin the molecule.The degree of bone uptake of DPD in rats is 15 %higher, and three hour whole blood retention of DPDaveraged o.2 % of the dose and is somewhat lowercompared with MDP. The boneâ€”toâ€”backgroundratio of DPDis therefore distinctly higher beginning at about 2hours after application. Whilst the femurâ€”toâ€”bloodratio of MDP is less than 25o three hours after injection, this value increases for DPD to more than 35o.The clinical trials, performed until now on about 3oopatients, showed a superior skeletal visualizationthan MDP.





STABILITY , STOICHIOMETRIC AND SITE CHARACTERISTICS OFGALLIUM BINDING BY TRANSFERRIN . M Raiszadeh J .F . Harwigand W Wolf. Radiopharmacy Program, University of SouthernCalifornia, Los Angeles, CA.

Upon intravenous administration, Gaâ€”67is bound, transported and transferred by transferrin (Tr). Despite thiskey role of Tr in tumor localization of Ga, little work hasbeen concerned with the structural characteristics of theGaâ€”Trcomplex. A combination of various techniques was empboyed to study stability and stoichiometry of the Gaâ€”Trcomplex,and effect of pH on the Ga binding sites in Tr.

Human Tr, 2.5 mg/mb, was incubated with gallium citratecontaining Gaâ€”67citrate at 37Â°and pH 7.4 in O.OO5M sodiumbicarbonate to give Ga:Tr ratios of 0.5â€”3.0,after whicheach was analyzed by gel filtration chromatography (CT),ultrafiltration (UP) and LW spectrophotometry at 245 mm.All three techniques indicated that only two Ga can bind toeach Tr. Similar experiments were carried out at a Ca:Trratio of 2 at various pH ranging from 4â€”7.5.The resultsshowed that at pH 7.3 both Ga binding sites in Tr can forma Gaâ€”Trcomplex, while at pH 5.5 only one specific bindingsite of Tr can form a Gaâ€”Trcomplex. The formation constants (k) of the Gaâ€”Trcomplex were determined by dialysisagainst DTPA. The average values for log k1 and k2 werefound to be 26.8 and 26.7 respectively, in very close agreement with literature prediction.

These studies demonstrate the importance of the structural features of the Gaâ€”Trcomplex in tumor uptake of Ga.For example, the properties revealed by pH changes may relect conformational features of Tr which are important inthe transferof Ga to or through the cell membrane. Onemight speculate that the pH dependence of the binding sitesmay result in easier release of Ga to the tumor cells fromthe binding site more susceptible to pH change.

BONE/JOINT

RADIONUCLIDE EVALUATION OF THE HIP SURFACE REPLACEMENTARTHROPLASTY WITH Tcâ€”COLLOID AND DIPHOSPHONATE. B.Thomas, H.C. Aastutz, L. Mai, N. Webber. University ofCalifornia, Los Angeles, CA.

Patients who underwent hip surface replacementarthroplasty were evaluated with technetiimi 99in sulfurcolloid bone marrow and technetiinn diphosphonate bonescintigraphy sequentially. The purpose was to determineif postâ€”operative complications can be detected andwhether these studies are useful in clinical management.Altogether 114 radionuclide scans on 55 patients (57 hips)who underwent total surface replacement(s) were studied.Each patient was studied first with bone marrow scan usingtechnetium 99m sulfur colloid and then with technetium 99inmethylene diphosphonate with a 3 hour interval betweeninjection and imaging. The scans of 39 of these patients(41 hips) with no known complications were compared to agroup of 16 patients with known complications (loosening,trochanteric bursitis, sepsis, and heterotopiccalcification). All scans were evaluated by areasaccording to a standard chart of the hip with each areasemiâ€”quantitativelygraded as to its uptake. The averagescore for each scan, group, and area were compared. Scansin the normal group appeared to be stable after 3months. Comparison of the two types of scans in thecomplication group showed decreased uptake of colboid andincreased uptake of techneti@ dipheaphonate andstatistically significant differences (delta values) werenoted as compared to the normal group.We conclude that the information obtained from bothstudies is more valuable than either study alone and thatthis technique is clinically valuable as a routine tofollow portâ€”operativesurface replacement arthroplasties.

RADIOISOTOPE LOCALIZATION IMMEDIATELY PRIOR TOPERCUTANEOUS BONE BIOPSY. R.N. DiSimone and W.J.Rowland. Northeastern Ohio Universities College ofMedicine, Canton, Oh

A technique has been developed for @accurate cutaneouslocalization of metabolically active bone lesions underthe Gamma camera with a Coâ€”57marker. Initially excisionab biopsies were performed to carefully evaluate this

localizing method. This proved to be very accurate sobiopsies were performed by percutaneous needle aspiration.The specimen is immediately examined by the cytopathobogist.

This study includes a total of 35 consecutive patientswho had positive radioisotope bone scans followed bybiopsies of the sites of involvement. A total of 50biopsies of metabolically active areas were performed.Although multiple areas of involvement on a bone scan inpatients with known malignancy usually indicate multiplemetastases, this may not always be the case. Of the 45adequate biopsies, 16 showed metastatic carcinoma, theremainder showed benign processes. Followâ€”upstudieshave not shown any false positive or negative resultswhen established criteria for specimen adequacy were met.

Because aspiration biopsies can be performed as anoutpatient and because biopsy results are almost iimnediately available, this procedure has gained acceptance byreferring physicians. The precise localization andbiopsy allows clinical decisions to proceed with greaterconfidence with obvious patient benefit, particularlywhen the active area is a benign lesion. No complicationshave occurred.

WWM@EBODY RETENTION: A COMPARISON OF ThREEDIPHOSPHONATES. I. Fogelman, A. J. Tote andN. D. Francis, Glasgow Royal Infirmary, Glasgow, Scotlandand The Procter & Gamble Ccmipany,Miami ValleyLaboratories, Cincinnati, OH.

Twenty normal volunteers had 2@Lâ€”hewwhole bodyretention(WBR)measurementsof theTc99mâ€”labeled(1â€”hydroxyethylidene)diphoaphonate (HEDP), methylenediphosphonate(MD!')and hydroxymethylenediphosphonate(IIIDP)skeletal imaging agents. Each volunteer receivedall three agents and the absolute skeletal uptake wasquantitated. The average WBR values were 18.11%,30.33%and 36.6% for HEDP, MDP and HMDP respectively. Thedifferences between the HEDPand MDPagents, and the I@DPand MDP agents at the 95% confidence interval was11.9Â±1.1%and 6.3Â±1.1%respectively.

The increase in I*1DPbone specificity, approximately20% greater than MDP and nearly double the HEDP value,clearly illustrates that slight alterations in thediphosphonate molecular structure have a significantCL.,'ct upon its specificity to osseous tissue.

HIGH JUXTAâ€”ARTICULARUPTAKE IN BONE SCANNINGâ€”A SIGN OFABNORMAL BONE MARROW DISTRIBUTION?H.G.A.Rydman,K-W.Beckman,K.J.VlkterlÃ¶f,B.G.H.Wadman.Urebro RegionalHospital,@rebro,Sweden.

97 patientswithdifferentlymphoâ€”myeloproliferativediseases were examined with whole body bone scintigraphy.40 of these patientswere also examinedwith bone marrowscintigraphy.

High juxta-articularuptakes and/or generalizedhighbone uptake were seen in 41 of 97 patients (1e2%). Thesefindingswere often very typicaland were most obvious Inpatientswith Chronic MyelocyticLeukemiawhere 16 of 19patients (84 %) demonstratedabnormal bone scintigraphy.

The high bone uptakeswere often well correlatedtoabnormal bone marrow distribution. In the knee regionthere was concordancebetween bone marrow and bone uptakein 35 of I@Qpatients.

Conclusion:Typicalbonescintigraphyfindingsinlymphomyeloproliferativediseases are often due to pathologicalextensionof bone marrow:

IPSILATEPAL ACTIVITY IN THE SHOULDER AREA ON BONE IMAGEAFTER MASTECTOMY: ITS SIGNIFICANcE. I.S. Seo, W.M. Sy,

C. chiarielbo, The Brooklyn Hospital, Brooklyn, NY.

Isolated increased activity in the ipsilateral shoulderafter mastectomy, especially when the joint is symptomatic,posed a problem in bone image interpretation. To assessthe significance of this activity, bone images in 251women who had mastectomy were reviewed and analyzed. Theincreased activity noted was either diffuse or distinct.Of the 251 patients , 44 demonstrated abnormal activity inthe shoulderarea, 31 unilateraland 13 bilateral. In

P78 Till JOURNAL. 01: NUCLEAR MEDICINE



PROCi.i.DINGS 01: TIll 28th ANNUAl. MIITIN(;

output, coronary blood flow and stroke work index areexpressed as a fraction of the control value.

This data indicates: (1) Normal pre-intervention EXTof the FFA is approximately 50% for both fatty acids; (2)EXT of both PTA decreases with hypertension and hypoxia.

FAILURE TO QUANTITATE VALVULAR REGURGITATION BY GATED EQUILIBRIUM R.ADIONUCLIDE ANGIOGRAPHY IN PATIENTS WITH DEPRESSEDLEFT VENTRICULAR FUNCTION. P. Nicod, J. Corbett,L.D. Hillis, B. Firth, C. Dehmer, C. Izquierdo,R. Markham,J.T. Willerson, S.E. Lewis, University of Texas Health

Science Center, Dallas, Tx.

In order to assess the accuracy of radionuclidedetermination of valvular regurgitation in the presence of severeleft ventricular (LV) dysfunction, we performed gated equilibrium radionuclide ventricubography (RVG) in 20 patients(pts) with LV ejection fraction (EF) @.35(meani24Â±.08,SD)and 48 pta with LVEF >.35 (mean @..65+.l2).Mitral and/oraortic regurgitation was present in 38 pts. RVG was performed in 15 pts at time of cardiac catheterization andat 9.4Â±12.9 days after catheterization in the others whilemedications and physical examination remained unchanged.Thirty pts had no regurgitation (23 underwent catheterization for coronary artery disease, and 7 were normal vobunteers). Stroke volume images were generated by subtracting the end systolic from the end diastolic frame. Theratio of LV to RV stroke counts was compared to the regurgitation fraction obtained at catheterization. The correlation between RVG and angiographic assessment of regurgitation was good for patients with LVEP >.35 (r.79; p.001). Conversely, in the group with depressed i@Vfunctiona similarly good correlation was not found (r.226; p. 339)and 11/20 pta were misâ€”diagnosed(2 with severe, 1 moderate6 mild, and 2 without regurgitation). Thus, RVG is accurate in evaluating regurgitation in pts with LVEF >.35but not reliable in pts withsevere LV dysfunction.

REGIONALEJECTION FRACTIONDURING EXERCISE: A QUANTITATIVEMEASUREMENTTO LOCALIZECORONARYARTERY STENOSIS.E.J. Brown, J. Wynne, B.L. Holman, and P.F. Cohn. Brighamand Women's Hospitaland Harvard Medical School, Boston,MA.

Westudied the ability of exercise radionuclide ventriculographyto localizecoronaryartery diseasewith regionalejection fraction (REF) analysis in 28 patients. REF is aquantitative radionuclide measurement derived from modifiedleft anterioroblique images of the cardiacblood pool andwas determined in anteroseptal and infero-posteriorsegmentsat rest and during exercise in patients with andwithout @.50%stenosis of the left main, left anteriordescending (LAD), left circumflexand/or right coronaryarteries (LCX-RCA). Results follow (mean Â±SEM):

@ <50%LAD(10) 2. @5O%LAD(18JRest anteroseptal .64 Â±.05 NS .66 Â±.04Exercise anteroseptal .74 Â±.06 <.05 .60 Â±.05

<50% LCX-RCA(12 @50%LCX-RCA(16)

.78Â± .06 NS .77Â± .05

.84 Â±.04 <.05 .71 Â±.05

In the anteroseptalsegment,only 2/10 (20%) patientswitha <50% LAD stenosis failed to increaseREF >5% (the normalresponse)while 13/18 (72%) of thosewith @.50%LAD stenosisfailed to increaseREF >5% (p < .01). In the inferoposterior segment,similar directional changeswereobservedbut were not statisticallysignificant. Inconclusion,although regions with and without coronaryartery disease tend to have the sameREFat rest, markeddifferencesare producedwith exercise. Thus, radionuclidelocalization of coronary artery disease is enhancedwhenregional function is measuredquantitatively.

ROLE OF B.ADIONUCLIDE ANGIOCABDIOGRAPHY IN CURRENT MANAGEMEN'r OF PATIENTS WIT!! ATRLAL SEPTAL DETECTS . R. Hurwitz , S.

Treves, R.Williama, N.Papanicolaou and A.Samuel. Children'sHospital Medical Center. Harvard Medical School. Boston. MA.

Radionuclide angiocardiography (RAC) and Mâ€”modeechocardiography (echo) have had increasing use in estimating left

27/31 the unilateral activity was ipsilaterab to themastectomy. In 9/13 with bilateral uptake, more intenseuptake ipsilateral to the mastectomy was noted. Two ofthese 13 with bilateral mastectomy showed equably intenseand symmetric activity. Hand images were also comparedand analyzed. Fourteen of 44 with shoulder activity alsodemonstrated ipsibateral increased activity in the bonesof the hand.

The ipsilateral shoulder activity was attributed to reflex sympathetic dystrophy (RSD) and periarthritis. RSDand periarthritis may follow trauma, coronary arterydisease, chronic lung diseases, and cervical spine syndromes. Trauma from mastectomy and the conscious or unconscious immobilization of the arm after the mastectomy werefactors considered to cause RSD or periarthritis in ourpatients resulting in the image abnormalities noted. Thehand features associated with the shoulder findings suggested disuse osteoporosis as a result of RSD. Degenerative arthritis or metastatic disease are excluded byradiographs or by presence of additional findings on thesame bone image.

CARDIOVASCULAR

COMPARISON BETWEEN EMISSION TOMOGRAPHYAND CONVENTIONALSCINTIGRAPHY IN TIlEDETECTION OF MYOCARDIAL INFARCTIONWITH THALLIUM-2O1. J. Maublant, J. Cassagnes, J.J. Le JeuneD. Mestas, A. Veyre, H. Jallut, C. Meyniel. Centre JeanPerrin et Hotel Dieu, Clermontâ€”Ferrand,France.

In a series of 64 patients showing a myocardial necrosis in any location, a comparison was made between emission tomography and conventional scintigraphy withthalliuinâ€”2O1.Each patient had presenteda myocardialinfarct between 4 days and 13 years before, fully documented by clinical, electrocardiographic, enzymatic and, insome cases, coronarographic evidence. The conventionalscintigraphic exploration was begun 10 mm after a 2 mCiinjection of thalliumâ€”2O1.Images of 500,000 counts eachwere collected by a GE 400 T scintillation camera underthe anterior, LAO 45 and left lateral views. Then 32 viewsof 30 sec each were acquired through a 180Â°rotationaround the left side of the patient. The reconstruction of10 to 20 adjacent transverse sections of 6.25 am thicknesswas performed by an Informatek computer using the filteredbackprojection algorithm. Frontal and sagittal sectionscould then be obtained from the transverse slices. Boththe conventional and tomographic images were interpretedindependantly by two observors without knowledge of theclinical problem. Using the scintigraphic images, thenecrosis was concordantly detected in 89 percent of thepatients, and in 98 percent with the tomography. The undiagnosed patient exhibitedan old, little infarctwith nopersistent electrical abnormality at the time of thescintigraphic exploration. These data suggest that emissiontomography with thalliumâ€”2Olis a more reliable atraumaticmethod for the detection of myocardial necrosis than conventional scintigraphy.

PreÃ§Fatty Acids (FFA) play an important role insupplying the energy needs of the myocardium under restcircumstances. Under the stress of hypoxia or duringmarked increase in blood pressure, the myocardium utilizesother substrates of metabolism and decreases its use ofFFA. We investigated the ?xtraction fraction (EXF) of Te123m-Heptadecanoic acid (Te) and 123-I-Hexadecanoic (I@acid by the canine@myocardium under control, hypertensiveand hypoxic conditions. The EXT was calcuJated by thedouble tracer method of Lassen and Crone with injectionof both the fatty acid and the reference substance (1-125albumin) in the left atrium and sampling in the coronarysinus. Hypertension was defined as mean blood pressureover 175 umiHg and hypoxia was defined as partial oxygenpressure between 20-SO umiHg. Results are shown as Mean@1 SD.

Rest inferoposteriorExercise inferoposterior

Volume 22.Number 6 P79

EXTRACTION FRACTION OF l23m Te-9-TELLURAHEPTADECANOIC ACIDBY HYPERTENSIVE AND HYPOXIC CANINE HEARTS. T Yasu4a F.PKn4pQ R Okada D Elmal?h K.A McKuaj@ck S KÃ§ipiwodaIDAiK V @[email protected],MA and OakridgeNationalLaboratory.Oak Ridge TN.

CONTROL HYPERTENSION HYPOXIAEXFâ€”Te(%,n5) 49.3Â±6.8 27.5Â±15.0* 33.2@ 6.3*EXT-I(%.n1) 50.5 33.0 32.6Heart rate 148.6Â±@4.8 176.5Â±18.1 138.8Â±60.9Mean B/P 89.5Â±16.7 188.8Â±13.1* 108.8Â±32.0Cardiac output 1.0 1.4Â±0.4 1.1Â± .7Coronary blood flow 1.0 3.1Â±2.1 2.0Â±1.2Stroke work index 1.0 2.4Â±1.1 1.6Â± .9*:p<O.OS when compared to the control value. Cardiac




to right shunt, represented by pulmonary to systemic flowratio (Qp:Qs) in patients with congenital heart defects.This study was undertaken to 1) evaluate the utility of RACin the current management of patientswith secundumatrialseptal defects (ASD); and 2) compare results from RAC toother nonâ€”invasivemeasurements. All patients with suspected ASD referred since 1979 for nuclide estimate of Qp:Qswere included.RAC was performedusing Tcâ€”99m(200 uCi/kg)or Irâ€”191m (200â€”800 uCi/kg) injected as a bolus into an cxternal jugular vein. Analysis was performed by a gameavariate method, using deconvolution.

There were 74 patients studied. All 15 who underwentcardiac catheterization or surgery within 6 months of RAChad good correlation between shunt calculation or measureaent of defect, and MC estimate of Qp:Qs. In these 15, RACwas superior to other nonâ€”invasivemethods for shunt estimate: Xâ€”raywas predictive in 8/13 performed; ECC was predictive in 11/13 performed; Nâ€”modeecho, using right yentricular dimension to estimate size of shunt, was predictive in 10/11 performed. In all 40 patients with both studice, echo results were less similar to those obtained byRAC; 32 had good correlation,while Qp:Qs was underestimated by echo in 2 and overestimated in 6. On the basis of resuits from RAC, 3 previously scheduled surgical procedureswere cancelled and 13 children were discharged from cardiaccare. The current study reinforces the use of RAC as aneffectivenonâ€”invasivetechniquefor estimationof leftâ€”toright shunt in patients with ASD.

INFERIORLEAD ST DEPRESSIONIN TRANSMURALANTERIOR INFARCTION: AN INDICATOROF EXTENSIVEGLOBAL AND REGIONALYENTRICULAR DYSFUNCTION. R. Levy, P.K. Shah, 14.Pichler, F.Shellock,D. Berman, H.J.C. Swan. Cedars-SinaiMedicalCenter, Los Angeles, California

The adverse Implicationsof precordiallead ST depression (l@)on left ventricular(LV) ejection fraction (EF)and regional (R) wall motion (WM) in Inferior (inf)myocardial infarction(MI) have been previouslydescribed. Todeterminewhether inf lead ST@(@lma) in anterior (ant) MIhas similar implications,LVEF, RWM, and right ventricular(Rv) EFwere determined In 35 pts within 24 hrs of firsttransmuralant MI using equilibriumradionuclideventriculography. The RWM of anteroseptal(ant-sep),inf-posterior(pos) and apical LV segments (segs)was assessed by a 6point WN score (S): 6Rnormal, 1=severedyskinesis. Results(mean+SD)were as follows:

EE WMS fn=seg number)LV RY All ANT-SEP INF-POS Apical

(10) (4) (4) (2)GrA .3O+,ll* .42Â±.14 35@4* 15+2* 18+3* 6+0.7(l9pts) â€” â€” â€”GrB .41+.1O .45+.l1 41+5 17+3 21+3 6+1.2(l6pts)@ â€” â€” â€” â€” â€”GrA=pts with lnf Sfl; GrBpts without lnf ST4.;*p<OO5Severe abnormalitiesof inf-postRWM were observed in 94%of ptsfromGrAcomparedto only36%of ptsfromGrB (p<0.05). The 30-day mortalitywas 16% In GrA compared to 6%in GrB. We conclude that pts with ant MI and concomitantinf â€˜eadSTI have greater global and regionalLV dysfunction than those without such ST@ and tend to have a highermortality. The high prevalence of severe inf-post WMabnormalityIn GrA suggeststhat Sri in inferiorleads mayrepresentadditionalinfero-posteriorlschesnicdamage.

ADDITIVE ABILITY OF TWO-VIEW EXERCISEYENTRICULOGRAPHYANDQUANTITATIVETl-2O1 ANALYSIS TO ACCURATELYASSESS THE EXTENT OF CORONARYARTERY DISEASE. A. Rozanski,J. Maddahi,E. Garcia, R. Levy, N. Pantaleo,A. Waxman and D. Berman.Cedars-SinaiMedical Center, Los Angeles, California

Since quantitative(Q) analysisof 11-201 stress distributton and washout and two-viewexerciseradionuclideyentriculography(ExY) representadvancementsin the scintigraphic (Sc) evaluationof coronaryartery (CA) disease(D),we studiedtheircombinedabilityto detectindividualCAstenoses (>50%)and multlvesseldisease (MVD) in 40 pts: 20with CAD and 20 normals (nfl. For QT1 analysis,maximalcount circumferentialprofilesof initialTl distributionand % washout at 4 hrs were used with automaticcomparisonto lower limits of ni. EquilibriumExY was performedinboth the 45Â°LAO and anterior views, and wall motion (WM)scored by a 5-point system (3=nl, _l=dyskinesis). Peakcx

ercise WM score(2 was consideredabnl. Sensitivity(Sn)and specificities(Sp) were as follows:

RCA (n=l7) LAD (nzl9) LCX (n=16) TOTAL (n=52)

@a@R@@

ExV 53 90 80 83 50 86 63 87QT1 74 83 68 79 50 86 61 83Both 84* 83 88 71 65 86 8O** 81*p 0.05 vs ExY; **p(0005 vs othersImportantly,while in this group ExY and QT1 each detectedonly 71% of the NVD pts (with a specificityof 88% for ExYand 82% for QT1), togetherthey detected 95% of the NYDpts (specificity of 82%). Thus, the combineduse of 2-viewExY and quantitativeTi analysis providesan accuratemeansof determiningthe presenceof individualcoronaryarterystenoses and is highly sensitive in identifying pts withmultivesseldisease.

RADIONUCLIDE DETERMINED PULMONARYBLOOD VOLUMEANDTHALLIUM LUNG UPTAKE IN PATIENTS WITh CORONARY ARTERYDISEASE. L.A yijaon R.D Ok@da cA Boucbe@. H,WStrauss G.M Pohoat. Massachusetts General Hospital,Boston,MA.

Exercise-induced changes in both r@dionuclidedetermined pulmonary blood volume (PBV@ and quantitativethalliuis-201 lung uptake in patients with coronary arterdisease (CAD).bave been correlated with increases in lefventricular filling pressure due to transle9t leftventricular dysfunction. The relative ability of thesetwo methods to detect LV dysfunction was assessed in 74patients (59 with and 15 without significant coronaryartery disease). Patients underwent supine bicycleexercise twice on the same day; first for thalliummyocardial (and lung) imaging and second for gated bloodpool imaging using Tc-99m labelled red blood cells. PBVexerciselrest (EX1R) lung ratios v@re abnormal in@42/59patients with CAD (sensitivity 71%) whereas thalliumlung/heart (Ti L/H@ ratio@ v@re abngrinal in 21/59 patientswitH CAD (sensitivity 36%), (P<O.O1). The specificity ofboth techniques was 100%. Age and resting ejectionfraction (EF) were not significantly different in normalversus abnormal Ti L/H or PBV EX/R ratios, However@abnormal Ti L/H and PRY EX/R ratios were both associatedwith decreases in EF from rest to exercise. There was asignificantly higher propranoiol (P) usage in the patientswifh abnormal Ti L/H ratios (9Q2) compared to patientswith normal Tb L/H ratios (51%) (p<O.Ol). No significantdifference in propranolol usage was present between normaland abnormal PBV EX/R ratios. Of the 15 normal patients.5 were on P and none bad abnormal Ti L/H or PBV EX/Rratios.

In conclusion, (1) both abnormal Ti L/H and PBV EX/Rratios are very specific markers of transient leftventicular dysfunction due to CAD during exercise. (2) Pdoes not appear @oalter the@specificity of Ti L/H gr PRyEX/R ratios. (3) The sensitivity of the Ti L/H ratio isless than the PRV EX/R ratio for patients with CAD.

CARDIAC OUTPUT FROM RADIONUCLIDEVENTRICULOGRAPHYDURINGREST AND EXERCISE. J.M. Marlette and R.B. Shafer. Veterans Administration Medical Center, Minneapolis, MN.

While the technologyexists for calculationof cardiacoutput (CO) from radionuclideventriculography(RNV),few publishedresults have appeared. CO calculatedfromfirst pass technique can only be performed during initialacquisitionand precludesexerciseor interventivestudiesuntil a later time. When calculatingCO from gated bloodpool acquisition,difficultiesarise in estimating @z,theattenuation coefficient, and d, the depth of the heart inthe chest for determining the attenuation factor [email protected] order to utilize first pass data, to avoid errors inattenuationcalculations,we proposed combiningfirst passand gated techniques. Using the CO calculatedfrom thefirst pass, a constant (K) can be derived from the gatedequationwhich is equal to the inverseof the product ofthe countrateper cc of blood and e@d. During exercise,(K) can be used to calculateCO (exercise). This eliminates errors in attenuation correction and in the samplingof activity per cc of blood.

Preliminarydata comparingrest and exercise CO withechocardiography,CO2 rebreathingand other non-invasivetechniquesshow good correlation. We conclude that calculationof CO from RNV is both practicaland costeffective.

I@PIFICATI@@ cw' MYOCAR@IALVIABILITY BY Th@NE7'1FNT INLFFP V@IQA@AR F@FICN IN@ RJ@E@ISE REO@TEB@YP@UOD. E.G. DePuey, G.P. Mmmem@, R.E. Sonneesker, A.H.Rivas, J.A. &irdime, R.J. Hall. Baylor cbllege of Medicinean@ St. La2ke'sEpiscxpalIbepital,}bus@n, TX.

P80 TIlE JOURNAl. 01: NUCLEAR MEDICINE



PROCILI)1NGS OF THE 28th ANNUAL MEETING

I@st1ng @.llnotion (*1) [email protected] are difficult toattribite to isd@nia vs scarrirs@ by electrocardiographic,angiographic, arsi rediora@clide tethniques. In tI@ earlyr@ery period fol].owin dynemic e@rcise vemtricular afterloed decreases@ to peripheral vav@is poolirq, t1@-retically decreasing n!@vcardial oxygen dmnarxi axxl thusischania. Tb investigate if ventric@ilar fuixtion irÃ§rovesdurirs this period as cxsi@ared to thu pro-exercise state,168 patients (pta) m@nittedfc@coronary bypass surgeryun1ex@nt resting , bicycle erercise (CC) , ard 3-6 mmpoet-exercise (PX) gated rediomaclide ventriculography.Within 3 @@iksfol1owii@ revascu].arizaticn surgery eachueder@nt a s@nd resting st*zly (P0) . Twenty-four arviographically mornal subjects @re also studied as ocntrols.Â¶Lt@efoll@iog ejection fractions (Â±@) @rethtaii@:

n R EX PX P0 p(R vs PX)

t@R4AtS 24 63Â±9 73Â±9 72Â±10 â€” <.001PATIPNPS 168 54Â±13 51Â±14 57Â±13 54Â±13 <.001

In 125 pta with alxs@rrnal R *1, *1 iitprov&I TX in 16, amiin 14 of thuse P0 (+ predictive value = 88%) . @ver,in 55 pta *1 1npro@ied P0 hut mot PX. In a subgroup of 23pta in s@un prenabire ventricular ocntracticns occurredangiography, *1 irproved in thu post-premature beat in 22.In the P0 isotope sttsfy *1 inproved in only 9 (+ predictivevalue = 41%). In [email protected] PX inpro@,emmntin *1 is a reliable predictor of rnyocardia.l viability. Absei@ of inprovei@t, iYJ/a@'er, canmot excbtxle Viability.

PATTERNS OF NUCLEAR CARDIOLOGY IN A METROPOLITAN COMMUNITT. S.M. Spies, L. Resnekov, G. Siamar. Chicago HeartAssociation Diagnostics Coninittee, Chicago, Illinois.

The purpose of this study was to better understand theutilization of nuclear cardiology in a large cousnunitythrough the use of a survey. A four page questionnaire wasdesigned to obtain information concerning hospital size,the types and volume of nuclear cardiologyproceduresperformed, the types of equipment used, the geographical location where examinations were conducted, the individualsresponsible for performance and interpretation of the varjous tests, and the experience and training of individualsinvolved in this activity. A total of 103 questionnaireswere sent within the Chicago metropolitan area to hospitalsranging in size from 137 to 1287 beds. Eightyâ€”threehospitals responded to the survey (80.62), and of these, 60(70.62) reported that nuclear cardiology services were aâ€”vaiiable. Tests were performed exclusively in the nuclearmedicine department in 47% of the hospitals responding,while in an additional 48%, the examinations were performedin both nuclear medicine and cardiology facilities. Theresponsibility of generating a final report lay with thenuclear medicine physician in 68% of the responses. Stressrelated procedures were supervised by a cardiologist in88% of the hospitals performing these tests. The most commonly performed examinations were Tc-99m pyrophosphate imaging, Tlâ€”201imaging, and multiple gated blood pool studies (88%, 87%, 672 of responding hospitals respectively).One third of the physicians responsible for interpretingthese tests have had formal training in the techniques.The unusually high response rate to this survey hasyielded an interesting perspective on the current practice of nuclear cardiology in this area.

EVALUATIONOF LEFT VENTRICULARFUNCTIONAND DETECTIONOFLEFT TO RIGHT SHUNTS WITH C15O@,.P1.Chevignd,L,Ouaglia,C.Detf'iore,3.11.Peters,P. Rigo. Cyclotron Research Center, University of Liege,Liege, Belgium.

Inhalation of C1502 delivers a bolus of labelled waterinto the pulmonaryveins and the left atrium; analysisofthe pulmonaryand left ventricularcurves providesan easymethod for the evaluationof left to right shunts and ofleft ventricular function.

The patient is seated before 6 collimatedprobes positioned toward the lungs. An additional probe is directedtoward the heart in a modified 15â€”20Â°left anterioroblique projection.Three to four mCies of C1502 are administared for study. We analyse the left ventricularcurve andcalculate the ejection fraction using a new method. Thebackground is first calculated for the cycle with largestdiastolic counts using characteristic points of the curvebefore and after transit of the indicator through the left

ventricle.For the other cycles, the backgroundis considared to be a constant fractionof the end-.diastoliccounts. Ef thus determined in 12 patients was highly reproduciblefrom beat to beat and from study to study inthe same patient (r = .94 and .97), It correspondscloselyto the ejection fraction determined using a camera computer system (r = .95). In patientswith left to rightshunts, the pulmonaryrecirculationis easy to recognizeand can be quantifiedga previouslydescribedby Watson,

We conclude that C1 02 inhalationis an attractivemethod to evaluate patientswith left to right shuntsand to assess left ventricularfunction.

RADIOIODINATED PHENYLFATTY ACID FOR MYOCARDIAL IMAGING.R.Dudczak, P.Angelberger, M.Wagnerâ€”LHffler,K.Kletter,R.Schmoliner, H.Frischauf.1st Med.Clin.,Dep.Nuci.Med.,Universityof Vienna,Austria

Fatty acids are an important energy source for themyocardium. Recently pâ€”phenylpentadecanoicacid (pâ€”PPA)wasproposed for myocardial imaging.

First the present report compares different HPLC purif iâ€”cation procedures for I 131 pâ€”IPPAand its biodistributionin mice and rabbits. This data indicated that labeledpâ€”IPPAcan be obtained in good radiochemical purity after asingle HPLC separation on a reversed phase system (LiChrosorb HP 18 lOim, 8x2SOnsn).A comparableaccumulationofI 131 pâ€”IPPAwas observed in hearts of mice and rabbits(t9min pi: .83% kg dose/g resp. .83% kg dose/g).In a preliminary study the imaging properties of I 123

pâ€”IPPAand Ti 201 were compared in pts with coronary arterydisease (CAD, nâ€”4)and with cardiomyopathy (CMP, n3).Scintigraphy (LFOV Searie, DEC PDP 11/34) was performedafter injection of 1 mCi I123pâ€”IPPA resp. 2 mCi T12O1

The scintigraphic results of Ti 201 and I 123 pâ€”IPPAdemonstratedcomparablefindings,and correlatedto coronaryarteriography. Irreversible and reversibleperfusion defectsobserved with Ti 201 stress scintigraphy in pts with CADcorresponded to regions of decreased uptake of I 123 pâ€”IPPA.Scintifotos could be obtained up to 40â€”60mm postinjectionof I 123 pâ€”IPPA.The myocardium/background ratio was superiorin Ti 201 scintigraphy. However a different kinetic behaviorof pâ€”IPPAwas observed in pts with CADcompared to pts withCMP. In pts with CAD tnaxmyocardial uptake occured earlierand the elimination half time from the heart was faster.

In conclusion I 123p4PPA might provide a potential alternative for investigations of myocardial perfusion, additionaliy revealing information about myocardial metabolism.

IMPROVEDACCURACY OF PHASE ANALYSIS FOR DETERMININGTHESITE OF ONSET OF VENTRICULARRHYTHMS. J. Friedman,A.Hamer, E. Garcia, T. Peter, W. Mandel, A. RozanskI,J.Maddahi, A. Waxman, and D. Berman, Cedars-Sinai MedicalCenter, Los Angeles, California.

While the phaseanalysis of Tc-99n1multiple-gated equilibrium blood pool scintigrams(MGES)might detect the siteof electricalactivation(SEA) in patients (pts) with spontaneousor paced ventricularrhythms,its accuracy in ptswith severe ventricularasynergy is unclear,as is the roleof the anterior (ant) view in evaluatingspatial orientation. Five pts with severe asynergy undergoingcoronarybypass surgery had 2 electrodes sewnto the right or leftventricularepicardiumless than 1 cm apart. Their anatomic location (AL) was related to appropriatelandmarks.Postoperatively,MGES was performedduring pacing in theant and 45Â°LAO views with slant-holecollimator. Acquisition was by an A2 MDS computerusing a 64x64 matrix and 32frames/cycleat 150K counts/frame. In 2 pts a shorteracquisition (20 frames/cyclefor 100 K counts/frame)was alsoused. Images were space-timesmoothed,and phase and amplitude calculationswere made using the first fourier coefficient. Three independentobserversdeterminedSEA fromphased images. In 2/5 pts the LAO view detected the AL;with addition of ant view, the AL was detected in 4/5 pts.There was no interobservervariability. Neither shorteracquisitionnor asynergy affectedaccuracyof SEA localization. Conclusion:1) Phase analysis can localize the siteof epicardial pacing even in the presence of severe asynergy; 2) the ant view improvesthe accuracyof the method;3) short acquisitiontimes do not appear to affect the accuracy, and may allow imaging of pts with unstable ventricular rhythms.




I'KxIIDIN(;S 01 TIll 28th ANNUAl. MIITIN(;

THALLOUS vrs THALLIC Tl-2O1: FACTORS INFLUENCING BIODISTRIBUTION AND )IYOCARDIAL TURNOVER. W.W. Hunter, N.V.Kulkarni,R. Price, Vanderbilt Medical Center, Nashville, TN.

Thallium (Tl)â€”2Olhas been used widely for myocardial perfusion studies despite reports of varibility in biodistribution and ignorance of the mechanism ofâ€•redistributionâ€•.We have investigated the marked differences in biodistribution of Tlâ€”2Olin rabbits and dogs produced by redox changes.Red blood cell and plasma distribution of Tlâ€”2O1were studjed in patients. In solution Tl is in equilibrium betweenthe thallous (I) and thallic (III) ions with the relativeproportions being strongly influenced by pH. Thallous ion,an analog of K+ is presumed to localizein the myocardium.Tlâ€”2Oluptake in the myocardium is increased by 25+%whenthe radiopharmaceuticalis combinedwith a reducingagentwhich shifts ionic equilibrium towards Tl@. An alkaline pHalso favors the formation of thallous ion and myocardial localization. Acidic pH favors the formation of thallic ion.Both the varibility in results from different lots of Tlâ€”2O1and the intracellular retention are probably related to pHchanges. Reduced intracellular pH in hypoxic regions of mycardium would promote the change from thallous to thallicion, an ion less likely to be diffusible across the cell rembrane. This would account for differences in the â€œredistributionâ€•phase. Like others of the III B group of the Periodic Table, e.g. Ga and In, Tl+3 may form hydrated colloids.This would account for an increase in the liver when the pHis reduced and an oxidant is added. TP3 tends to form complex ions. These would explain our findings of variable distributionto the thyroid and RBCs. Indeed a significant2ortion of the plasma activity in patients receiving Tlâ€”2Olisanionic when separated by ionâ€”exchangeresins. These changesin the valency state of Tl which affect the distribution tothe myocardium and other organs and changes in circulatingbackground can be manipulated for clinical benefit.

LACK OF CLINICAL UTILITY OF INCREASED LUNG THALLIUM UPTAKEIN PREDICTING MULTIVESSEL CORONARY ARTERY DISEASED.M. Mccarthy, P.T. Makler, Jr. , A. Alavi, J.A. Kastor,Hospital of the University of Pennsylvania,Philadelphia,PA

It has been reported that patients (pts) with increased

thallium activity in the lung on post-exercise images arelikely to have severe coronary artery disease (CAD). Thisphenomenon was prospectively evaluated in 54 pta (l4=noCAD, 20=lV CAD, l3=2V CAD, 7=3V Ciw). Images were obtamed at 8 mm and 4 hr after peak exercise. Lung activity on the 8 mm anterior image was qualitatively gradedas little or none (23 pta), 1+ (20 pta) or 2+ (11 pts) bytwo blinded observers. Count rates per unit area werequantified over the lung and the washout rate was determined as the ratio of these count rates in the early andlate images.

The 11 pts with 2+ lung activity had significantlygreater digitalis use and lower double product (HR x BP)during exercise (p<.O2). The lung washout rate was alsohighest in this group. However, there was no significantdifference in the resting left ventricular ejectionfraction, left ventricular end diastolic pressure ornumber of diseased coronary vessels (1.8Â±1.1vs 1.1Â±1.0,pNS). Among all pts there was no significant correlationbetween lung washout rate and number of diseased vessels.

We conclude that while increased lung thallium activityon post-exercise images may be a consequence of exerciseinduced left ventricular dysfunction, its presence doesnot predict multiveasel CAD.

THE MARKEDLYABNORMALEXERCISE RADIONUCLIDEANGIOGRAPHICRESPONSEâ€”AMARKER OF CRITICAL CORONARY DISEASE. R.J. Katz,A.G. Wasserman, V.M. Varma, R.J. Reba, A.M. Ross. GeorgeWashington University Hospital, Washington, DC.

To maximize the nonâ€”invasiveprediction of high riskcoronary disease (CAD) we examined the quantitative significance of a markedly abnormal response to exercise radionuclide angiography (EXRNA) defined as an exerciseâ€”inducedfall in ejection fraction (EF)>5%. One hundred sixteenconsecutive pta who underwent supine EXRNA and coronaryarteriography were grouped anatomically: group 1 (nl9)>50% stenosis of the left main coronary artery; group 2(nâ€”431)>70%of stenosis of 3 coronary vessels; group 3(n@l9)>7OX of 1 or 2 vessels but including >90% stenosiaof the left anterior descending. The remaining 35 pta

had minimal or no CAD.A marked fall of EF>5% was seen in 44/116 (38%). This

markedly positive EXRNA response was found in 31/62 (50%)of pts in groups l&2 and 41/81 (51%) of pta in groupsl,2&3. The predictive value of this markedly abnormal response for group l&2 anatomy was 31/44 (70%) and for groupl,2&3 anatomy was 41/44 (93%). Only 3/44 (7%) with EXRN&Er fall@ did not have severe CAD.

In 67 pta exercise treadmill tests (ETT) were also performed. Severe CAD (group l,2&3 anatomy) was angiographically documented in 49/67 (73%). A markedly abnormal ETT(defined as either exercise induced hypotension or ST depression>2umi) identified 18/49 (34%) of these high riskpta; whereas the markedly positive EXRNA identified anadditional 17 pta (combined sensitivity 69%).

Conclusions: (1) A marked fall in EF during EXRNA ishighly predictive of high risk coronary anatomy. (2) EXRNAadds considerably to the sensitivity of standard ETT forthe detection of critical CAD.

QUANTITATIVE RADIONIJCLIDE ANGIOCRAPHY TO ASSESS CIRCULATORYCHANGES DURING UPRIGHT EXERCISE IN PATIENTS WITH POOR LEFTVENTRICULAR FUNCTION. A.S. Iskandrian, A.H. Hakki, M.N.Croll, S.A. Kane, B.L. Segal, D. Kimbiris, C.E. Bemis, andc.S. Mintz. CardiovascularInstitute,HahnemannMedicalCollege and Hos@ital, Philadelphia, Pennsylvania.

We studied 40 patients (pta) with poor left ventricular(LV) function (ejection fraction <40%) by using symptomlimited upright exercise (EX). 50% of the pts had infarction (MI). We obtained firstâ€”passradionuclide angiogramsat rest (R) and peak EX using a multicrystal camera.Twelve normal subjects (ML) served as a control. There waspoor correlation between the duration of EX and the restingLVâ€”EF(r â€”.28). Twenty of the 40 pta shoved an increaseof <20 mm Hg in systolic blood pressure (BP) during EX; allMLshoweda riseofgreaterthan20mmHg(p< 0.001).There were insignificant changes in the EF during EX in ptawith or without MI (27@ 7@ at R vs 27@ 8% at EX, and 25@7% at R vs 27@ 8% at EX, respectively). In 26 pta, volumemeasurements were available; there were insignificantchanges during EX in the endâ€”diastolicvolume (EDV) andstroke volume (SV). In these pta, the change in the cardiac output (CO) (5.6@ 2.5 liters/mm at R vs 9.9 Â±4.3 atEx,@ < 0.001) was predominantlydue to an increase in theheart rate (HR). The hemodynamic changes are significantlydifferent from ML in whom the increase in CO was due to bothincrease in SV and HR. We conclude: In pta with poor LVfunction: 1) Ex tolerance cannot be predicted from the resting LVâ€”EF;2) the increase in CO during EX is related tochanges in the HR, since neither LV dilatation nor an increase in EF is conuson; 3) the modest increase in the CO andsystemic vasodilatation during EX result in a modest increase in BP (<20 tenHg) in 502 of the pta; 4) the changesin EF during EX are not related to the presence or absenceof prior MI.

QUANTITATIVE ASSESSMENT OF ISCHEMIC MYOCARDIUM IN PATIENTSWITH ONE-VESSEL DISEASE: EFFECT OF COLLATERALS. A.S.Iskandrian,M.N. Croll, R. Lichtenberg,B.L. Segal, G.S.Mintz, A.H. Hakki, and S.A. Kane. CardiovascularInstituteHahnemann Medical College and Hospital, Philadelphia, PA.

The size of the perfusion defect (PD) was assessed usinga quantitative analysis (QA) of exercise thalli'imâ€”2Olimages (ETI). QA was performed by measuring the area andthe terimeterof the PD and expressingit as a percentageofthe total left ventricular (LV) area or perimeter in eachprojection. We studied SO patients (pta) with oneâ€”vesseldisease (1VD) of >50% diameter narrowing. Of the 11 ptswith 50â€”69%narrowing, only one Pt had abnormal ETI. Of theremaining 39 pta with >70% narrowing, abnormal ETI was seenin 35 pts (all 16 pta with left anterior descending disease(LAD), 10 of 12 Pta with left circumflexdisease (LCD),and9 of 11 pta with right coronary artery disease (RCA)).There was good correlation between the planimetric and theperimetric methods (p < 0.001, r â€”0.97). There was markedvariation in the size of the PD in the three groups of pta.The PD (average of three standard projections) was largerin pta with LAD (33%@ 10%, mean + 1SD) than in pta withLCD (191 + 14%), and in pta with RCD (7% + 11%, P <0.01each). The size of the PD did not correlate with the degreeor site of narrowing. Pts with LAD but with collateralshad smaller PD than their counterparts without collaterals

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PROUFII)INGS 01 TIll 28th ANNUAl. MEETING

(25% + 6% vs 40% + 8%, P < .001).We conclude: (1) There is marked variability in the size

of the PD in pta with 1VD. Pta with LAD have larger defectsthan pta with LCD and RCD. This aimple method of QA maythus be useful in identifying pta at high risk. (2) Collaterals offer partial protection during exercise by limiting the size of the PD. The beneficial effect of collaterals was only evident by quantitative analysis.

ABNORMAL THALLIUM SCANS IN ThE ABSENCE OF SEVERE CORONARYARTERY DISEASE. A.S. Iskandrian, S.A. Kane, A.H. Hakki,B.L. Segal, and M.N. Croll. Cardiovascular Institute,Hahnemann Medical College and Hospital, Philadelphia, PA.

Abnormal exercise thalliumâ€”2Olscans, in the absence ofsevere coronary artery disease (CAD), are generally regarded as falseâ€”positive. We examined the causes of falsepositive scans in 45 consecutive patients (pta) with chestpain syndrome, who, according to the results of the cardiaccatheterization, were divided into: Group I (15 pta) hadnormal studies; Group II (20 pta) had either insignificantCAD (less than 50%; 15 pta) or a small left anterior deacending artery (LAD) (2 pta) or coronary ectaaia withoutstenosis (2 pta) or anomalous origin of the right coronaryartery (RCA) from the pulmonary artery (1 pt). The remaining pta comprised Group III and had mitral valve prolapsewith normal coronary angiograms. Eight pta (18%) had abnormal exercise thallium scans; one pt in Group I (7%), onein Group III (10%), and 6 pta in Group II (30%) (2 pta withmild CAD, 2 pta with small LAD, 1 pt with ectasia, and 1 ptwith anomalous origin of RCA). The defect was in the distribution of the diseased vessel in each pt. Eight pta hadpositive exercise ECGs (5 of the 8 pta also had positivescans). Of these 8 pta, 3 were in Group I (20%), 3 were inGroup II (15%), and 2 in Group III (20%). The eight ptaexercised to at least 85% of the predicted maximal heartrate. We conclude: abnormal scans in the abaence ofsevere CAD are not truly falseâ€”positive. They can be cxplained on the basis of coronary spasm (in pta with normalangiograma or insignificant CAD); underestimation of theseverity of CAD by angiography, coronary ectasia, abnormalanatomy of the coronary vessels, or prolapse of the mitralvaivc.

[email protected],J. ca.rrrody, S. thelsy, J. Fain.Division of Nuclear Medicine,I1AC Harbor-UcLA Medical Center, lbrrance, CA.

Phaseanalysis evaluates at frequent tirno intervals , thedynamic status of each pixel Iran inforrration acquired byE@l equilibrium asiltigated studima or sequential framesfrom non-cardiac dyntsnic studies . In cardiac studies thedistribution of elanents ccsprising the phases of ventricular es@tying or filling is displayed on a 360 @gree colorscale using first harmonic information obtained frcm eachpixel via fast Fourier analysis. Diastole and systoleappear separated by approxinmxely 180 degrees and are represented by opposite colors, providing an outstandingdefinition of atria fran ventricles. A normal heart iscI@ac@terized by synchronous aiptying of the differentventricular regions , depicted by a narr@ band of colordistribution, being the narrowest at high ejection fraction(EF), and disorganizedat low EF. In 60 patientscorrelation between the standard deviation of the mean pixeldistribution (HEMP!)) in ventricular systolic phase and theleft ventricular HF was 0.83. At HF of 62Â±5% the SL@1PDwas48Â±1.5Â°. At EF 20-50% the SDMPD is 8.1Â±1.7Â°,HF less than2c@, 10Â±30. Patterns of ventricular esptying and electricconductivity abnormalities are correlated with myocardialcontraction patterns observed in gated FD3 thalliun-2Olmyocardial scans. Phase analysis is efficacious in thefollowing cardiac areas : 1. definition of cardiac valveplanes for valvular regurgitation studies , 2 . daixnstrationof ventricular aneurymes , 3. ventricular edge definition,4. analysis of progression of ventricular excitation, inpatients with electric conductivity abnoram.lities. It isused also in analysis of renograns and lung clearances ofaeivsols. It is therefore a useful adjunct to left ventriculography and other areas of nuclear medicine.

COP@BINEDUSE OF TWO SCINTIGRAPHICTECHNIQUESIN THE IDENTIFICATIONOF REVERSIBLEMYOCARDIALASYNERGY: COMPARISONTO

THE ADMINISTRATIONOF NITROGLYCERIN. A. Rozanski,0. Berman, R. Levy, J. Maddahi, E. Garcia, J. Gutman, A. Waxman.Cedars-SinaiMedical Center, Los Angeles, California

Since reversibilityof myocardialasynergy (asyn)may bepredictedby either improvementof wall motion (WM) mmcdiately post-upright exercise (IMPEX) or a normal (ni) Tl-2O1(Tl) redistribution(RD) pattern in asyn segments (segs),we sought to compare the combinedability of IMPEX radionuclideventriculography(RNV),performedafter2-viewsitting bicycle exercise,and Tl stressâ€”RDscintigraphy(Sc)to differentiatereversible(R) from nonreversible(NR)asyn. Thus, 20 consecutIve pts with resting asyn undergoing both Sc tests also underwentresting RNV before andafter nitroglycerin(NTG). For both 11 and RNV, anteriorand 450 LAO imageswere divided into 5 segs. WM was assessed by a 5-pointsystem: 3=nl, -l=dyskinesis. FollowingNTG or IMPEX R asyn was consideredpresent if asyn WM=3 orincreased>2 from control;otherwiseasyn was NR. For eachseg, the Tl-RD patternwas deemed nl or abnormal (abnl) byconsensus of 3 blinded observers. Results:

NTG RESPONSEIl-RD IMPEX WM R Asyn (n=25 se@s NR Asyn (n=30 segs)

@ R 21 1Ni NR 3 8

Abnl R 0 0Abnl MR 1 21

Thus, the combination of nl Il-RD and improved WNIMPEXis highly predictiveof R asyn followingNTG; similarly,combinedMR WM IMPEX and abnl Il-RD is equally predictiveof MR asyn. Therefore,the concordanceof these test results allows for the accurate scintigraphicdifferentiationof reversibleand nonreversibleasynergy.

ASSESSMENT OF RIGHT VENTRICULAR TL-2Ol STRESS AND EARLYREDISTRIBtTrION SCINTIGRAPHY : A METHODFOR DETECTING PROXIMAL RIGHT CORONARY ARTERY STENOSIS. M. Brachxnan, J. Gutman, A. Rozanski, D. Tanaseacu, L. Ramanna, A. Abdulla,J. Maddahi, A. Wa@anan, and D. Berman, Cedars-Sinai MedicalCenter, Los Angeles, CA.

Since the right CR) ventricle CV) is supplied almost cxclusivelyby the proximal (p) R coronaryartery (CA),stress RV Tl-20l (Tl) abnormality (abnl) might be indicative of p RCA stenoais (at). Thus, we evaluated the resulta of angiography in 42 pta also undergoing stress andearly (45 minute) redistribution CR0) Tl imaging, including21 pta with p RCA at ()5O%) (group I), and 21 pta without pRCA at (group II). Two criteria for abnl were evaluated.An initial defect was defined by a decrease in distal RVfree wall Tl uptake compared to the proximal wall. Delayedvisualization (DV) was considered present when the RV wallin early RD 45Â°LAO image was as bright as or brighter thanthe stress image. Since the RV was not well seen in the 4hr RD images (37/42 pta) , these images were not used foranalysis.

In group II pta, no focal RV defects were present, butDV was present in 9 of the 21 pta. In contrast, 18 of the21 pta in group I had evidence of DV and 5 of the 21 ptademonstrated stress RV Tl defects. Of note, the inferiorwall of the left ventricular acintigrams was N in 2 of the5 withRCAatandRVdefects.

Thus, the presence of a stress RV Tl defect is highlyspecific although relatively insensitive in the detectionof p RCA st. In complementary fashion, the presence of delayed visualization of Tl in the RV during early RD is aensitive but not specific in detecting p RCA at. Evaluationof the right ventricle should thus be performed during theinterpretation of stress Tl-2Ol scintigraphy.

ASSESSMENTOF PULMONARYVASCULARREACTIVITYBY RADIONUCLIDEANGIOCARDIOGRAPHY. A.M. Fujii, N. Rabinovitch, J.F. Keane,D.C. Fyler, S. Treves. Children's Hospital Medical Center,Boston, Massachusetts 02115.

We applied radionuclide angiocardiography to assesspulmonary vascular reactivity in 8 patients with large,relatively unrestrictive intracardiac defects and pulmonaryhypertension. Using technetium 99m pertechnetate, radionuclide angiocardiograms were performed first with thepatient breathing room air and then after 10 minutes of

90% oxygen. The pulmonary to systemic flow ratio obtained by the gaa variate analysis of the radionuclide timeactivity curves were compared with those calculated by the

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PR()CIII)IN(;.s OF Tilt 28th ANNUAl. MELTING

Fick principle at the time of cardiac catheterization. Atotal of 9 studies were obtained (one patient was evaluatedon 2 separate occasions , several months apart) . There wasa good correlation between the two methods both in room airstudies (r, .88) amA in those obtained in@ 90% oxygen(r,.94). All 6 studiesof patientswitha reactivepulmonary vasculature (judged by a pulmonary vascular resistanceat cardiac catheterization@ 6 units/in2 in oxygen or aftertolazoline), had radionuclide pulmonary to systamic flowratios@ 3.0 in oxygen. The 3 studies of patients with anonreactive pulmonary vasculature had a radionuclidepulmonary to systemic flow ratio@ 2.3 in oxygen that wasunchanged from the room air value . These data suggest thatradionuclide angiocardiography may be a useful, relativelymoninvasive way to assess pulmonary vascular reactivity inpatients with large, relatively unrestrictive intracardiacdefects.

PHASE IMAGE CHARACTERIZATION OF VENTRICULAR CONTRACTION INLEFT AND RIGHT BUNDLE BRANCh BLOCK . MA Frais , EHBotvinick, OW Shosa, JW O'Connell, B Levin, RS HattnerUniversity of California, San Francisco, CA

Phase (Ph) analysis (A) was used to characterize mechanical and electrical activation sequences of the right (R)and left (L) ventricles (V) in patients (pta) with bundlebranch block (BBB). Equilibrium blood pool scintigraphy(5) was performed in anterior and â€œbestaeptalâ€•LAO projectiona in 16 pta with normal ECGa (N), 4 pta with LBBB and 6pta with RBBB, all with normal wall motion. Ph images (I)were obtained by fitting the S data with the fundamentalFourier harmonic and were displayed as composite static anddynamic Ph I, and a Ph histogram of each visually determmed ventricular region.Dynamic Ph I demonstrated nearly simultaneously Ph varia

tion of both V in N, an abnormal LV contraction sequenceand visual LV delay in LBBB and an abnormal RV contractionsequence and RV delay in RBBB. Calculated were the meanPh (PTi)and mean SD of Ph(SD) of LV and RV in N, LBBB andRBBB and the mean Ph difference, LVâ€”RV.

Results : Ph: LVNv5LVLBBB@ .8Â°Â±ll.3Â°vsl6.2Â°Â±lO.7Â°(NS);

Ph: RVNvaRV@BB 12.9Â°Â±ll.8Â°vs28.9Â°Â±l5.4Â°(p<O.05);

SD: LVNvsRV@BB 20.10Â±5.5Â°vs2l.7Â°Â±2.2Â°(NS);

SD: RVNvsRV@BB 28.6Â°Â±lO.2Â°vs27.6Â°+6.OÂ°(NS);

Ph: (LV_RV)@BBva(LV_RV)Nvs(LV_RV)@BB

2O.40+9.8Â°vsâ€”5.lÂ°+6.6@(p<O.OOl)vs _25.O0Â±ll.l0(p<O.001)

PhA of BBB demonstrates a relative delay and abnormal contraction sequence in the affected V but does not demonstrateincreased intraventricular Ph dispersion.

RESTING LEFT VENTRICULAR EARLY DIASTOLIC FILLING IN NORMALSUBJECTS AND PATIENTS RAVING CORONARY ARTERY DISEASE. A.J.Kemper, J. Polak, J.A. Bianco, A.F. Parisi and D.E. Tow.West Roxbury VA Medical Center, Harvard Medical School,Boston, MA.

Resting left ventricular (LV) early diastolic fillingwas assessed in 40 subjects by fitting a fourth order polynominal function to first pass timeâ€”activitycurves obtamed with a multicrystal system at 25 macc. temporal resolution utilizing as onset of diastole the nadir in LVcounts. Control subjects (Nâ€”b)were compared with coronary patients with (I) (Nâ€”16)and without (II) (N14) angiographically defined LV wall motion abnormalities. Controla had a significantly shorter time to peak filling (141Â±39macc.vs 182Â±47 (I) and175Â±32 (II), p < .01 forboth) and a higher peak filling rate (2.28 Â± .59 EDV/aec vs1.08 Â±.22 (I) and 1.4 Â±.35 (II), p < .001 for both) thaneither of the patient groups. Although time to peak fillingwas not a useful predictorof coronarydisease in the mdividual patient, an abnormal peak filling rate was found inall patients with previous infarction and in 71% of coronary patients who had normal LV systolic function when thelowest control value (1.65 EDV/aec) was used as a discriminator.

Our data suggest that abnormal left ventricular compliance is easily demonstrable during rapid ventricularfilling in most patients with coronary artery disease.

Analysis of resting peak filling rate may offer a simplemethod for the detection of coronary artery disease in patients with otherwise normal LV function.

D@NN4IC BICYCLE Nt@ IS@lE@IC [email protected] EXEI@ISE IN P1TI@N1Swmi @ci@ricn@icm@c@. E.G.DeTh.iey,R.E.Sonnaimker,R.J. Hall, l.A. @irdime,Baylor cbllege of Medicine ard St.Luke's F@isenpa1 Ibepital, Houston, â€˜1%.

In patients (pta) with mortic insufficiency (AX) t1@ degrme of left v@trioi1ar dysfuixtion nay determine the cptiinaltJimefor surgical intervaition. @lb @ared@ia@cbicycle ex@cise (BK) aed iscme@ic hardrip exercise (HG)in t1@ir ability th elicit vemtrioular dysfizwrtion, 15 ptawith AX aed r@ otter valvular or omrcnary disease w@welt gatal redion@x:1ide ve@triculography durirs BK arx@ HGin t]@ 45 sitting @xsiticn. 1Xirir@ @Cthe @wk1oed wasincreased by 100 JcEm@every 3 mdii to tI@ point of s@m@txxi@or fatigue. HG was sustained at 25% of naxinun effort totI@ limits of fatigue or a nmxinun of 6 nd.n.@ averagerate-pressure pz@:d@rts (x102) attaimed ware 279.5 Â±(@@)for BKarsi164.6Â±42.1fc@HG. @I1@cthangein ejection fraction fran resting to peak exercise (6@Y) was compared to exxlsystolic inirxr diameter neaswed ectxgraphically in 11 pta (Râ€”O.63for BK; [email protected] HG), to left v@itricular eral diastolic pressure measured by catheterizationin 8 pts (Râ€”O.84for BK; [email protected] for HG), med to the degreeof regurgitation (1-4+) estimated visually durirs@enntrastv@triculography in 12 pta (R0.27 for BK; R.0.30 for HG).BK A@P correlated linearly with systolic dianeter az@ diastolic pressure, A.@Pbecoming negative at 4.9 an diweter or16.7 amHg. HGA@'did zxt ctharsjein patients with systolic dia@@ters â€˜:5.0art, arvi ervi diastolic pressures <16 meHg. With more abt@@rrra1parameters of ven@icu1ar futxfticn,the HG AEP became progressively negative. In cosxlusion,AFT durir@ BK med HG @rre1ate poorly with the degree ofregurgitation, but fairly wail with other wail-recognizedparameters of v@ltrion1ar dysfuix,tion in pta with AX.

SERIAL RIGHT VENTRICULAR THALLIUM-201 IMAGING FOLLOWINGEXERCISE: RELATIONSHIP TO RIGHT CORONARY ARTERY DISEASE.l.A Bjoyn C,A Igupher @.W Strauss .A N ai4s.D OkaÃ§@; G.M Pohost. Massachusetts Genera ospital.Boston, MA.

The right ventricle (RV) is frequenÃ§ly well defined onmyocardial thalliua-2Ol imaging following exerctse. Therelationship of RV thallLme-201 distribution to rightcoronary artery anatomy and left ventricular (LV) inferiorwall thallium distribution was examined in 88 patientsfollowinggraded treadmillexercise. Thallium-20limageswere recorded 5-10 minutes and 2-3 hours after exercise inthe anterior and left anterior oblique positions, and theRV and inferior LV wall were interpreted as normal grshowing transient defect (TD) or persistent defect (PD).

The RV image showed TD in 8 patients; 8/8 (100%) had>90% stenosis of proximal or mid right coronary arteryâ€¢rP/NRCA), and all bad TD o@ PD of @.nferiorwall. The RVshowed PD in 10 patients; 9/10 (90%) had @5O%stenosis and7/10 (70%) had @9O%stenosis of P/N RCA, although inferiorwall was nprmal in 5/10. Of 70 patients with pormal RV,29/70 (4l% bad P/N RCA disease (@?.5O%steqosiq). Whenboth RV and inferior wall were normal, 10140 (25%) had P/Nor distal RCA disease.

The sensitivtty/speciftcity was then examined. Of the88 patients,46 hadP/NRCAdisease,7 haddiseaselimitedto the distal portion and 35 had normal RCA. For P/N @CAdisease, the sensitivity was @7%for RV imagj.ng (TD+PD),67% for inferior wall defect (TD+PD) (p<.OO5). Combined RVand inferior yall sensitivity was 78% (pNS, compared withinferior wall). For distal RCA disease, the sensitivitywas 0/7 for RV imaging and 6/7 for inferior wall(pc.0001). The specificity for RV defect was 98% comparedwith 86% for inferior wall (pc.O5), and 83% for combinedRV plus inferior wall (p<.Q51.

Thus, with serial thalliust imaging following exercise:(1) Transient defect and persistent defect of RV arehighlyspecificforP/NRCA4sease andaremorespecificthan inferior wall defect; (2) Transiept defect of RV ishighly predictive for@high grade (>90%) stenosis of P/NRCA; @3)the sensitivity for PIN disease was significantlylower for RV comparedwith @.nferiorwall defect; (4) acombination of a normal RV image and LV inferior wall didnot exclude RCA disease.

ENDOCRINE

EFFICIENT THYROID SCINTIGRAPHY. T.R. Simon, J. Keith,S.E. Lewis. University of Texas Health Science Center,Dallas, Tx.





The thyroid is best studied with iodine; however, costand convenience have lead to the widespread use of Tcâ€”99mpertechnetate (TcO4) . Since 97% of our thyroid referralsrequest a combined radionuclide uptake determination (RAIU)and scintigraphy, a protocol using a single, small oraliodineâ€”123dosewas instituted.StandardTc04imageswerealso performed. Images were obtained using a 100,000 countpinhole technique. The iodine images were obtained 24hours after an oral dose of l5OuCi; and the Tc04 images,20 minutes after lOmCi I.V. Both radioisotopes requiredabout 10 minutes of acquisition time. All patients studied from 5â€”1â€”78to 2â€”28â€”79were collected. Of these, 107had the pathologic, ultrasonic, or twelve month clinicalfollowâ€”uprequired for diagnosis. Five groups were established: 1) solitary lesion, 2) Graves', 3)aultinodulargoiter, 4) normal, and 5) other. The patient distributionwas: 9, 23, 40, 24, and 11, respectively. Retrospectiveanalysis proved the diagnostic usefulness of the technique;the percent sensitivity/specificity for the group was 100/92, 96/99, 80/98, 96/98 and 82/100, respectively. Twonuclear medicine physicians reâ€”interpretedthe studieswith concurrent iodine and Tc04 images. The diagnosticvalue of the images did not significantly differ betweenthe radiopharmaceutical used: the sensitivity/specificitywas (TcO4) 95/93 and (1â€”123)100/91.

Thus a single low dose of 1â€”123suffices for a combinedRAIU and thyroid scintigraphic study to provide the benefits of high diagnostic accuracy with an ideal imagingagent while avoiding unreasonable cost and inconvenienceto the patient and the diagnostic laboratory.

CRITICAL EVALUATIONOF SERUM THYROGLOBULINLEVELS AND 1-131SCANS IN POST-THERAPYDIFFERENTIATEDTHYROID CARCINOMAPATIENTS. R.L. Echenique,L. Kasi, T.P. Haynie, H.J. Glenn,

N.A. Samaan, and C.S. Hill. The Universityof Texas SystemCancer Center N. 0. Anderson Hospitaland Tumor Institute,Houston, TX.

Serum thyroglobulinmeasurementsby radioimmunoassaywere performed in the follow-upof 68 patientswith differentiated thyroid carcinoma undergoing iodine-l31total body scan followingsurgery and/or iodine-l3ltherapy. Of the twelve patients with distant metastasisdemonstratedby 1-131 scan, thyroglobulinlevels wereelevated (>60 ng/ml) in 9 (75%) of the patients; theremaining 25% had either normal (20 to 60 ng/ml) orsubnormal (20 ng/ml) levels in spite of having functioning metastasis. In 6 patients with only regionallymph node metastasisdemonstratedon 1-131 scan, only 1(16%) had an elevated thyroglobulinlevel, while 2 patients had normal and 3 patients had subnormal thyroglobulin levels.Of the remainingpatientswith no metastatic disease demonstratedby 1-131 scan, 3 had elevatedthyroglobulin levels (6%). These 3 patients weresubsequentlyfound to have metastaticdisease by othercriteria. Case reports illustratesome reason for thislack of correlation between the two tests. In thesepatients, both tests were often necessary to achievemaximum sensitivityand reliability. These results suggest caution in the use of thyroglobulinlevels as areplacement of 1-131 scans in the follow-up of differentiated thyroid carcinoma.

INCIDENCE OF THYROTOXIC GRAVES â€D̃ISEASE IN PRISONERS â€¢H.M.Park, LA. Young, R.D. Bamsgartner,IndianaUniversityMedical Center, Indianapolis, IN.

Severe emotionalstress or acute fright has been suggested as a possible trigger for clinicallyevident Graves'disease (Ingbar ,p â€¢199 ,The Textbook of Endocrinology,Saunders.1968). On the other hand, behavior dysfunctionmay occur in Graves â€d̃isease patients which can Improvewith treatment (Rockey, Arch.I.M.l40:ll94,l98O) . Daviset al reported 3 crIminals cosmiitted felonies while syaptowatically thyrotoxic (Ann.Int.Med.74:743,197l).

We investigated the incidence of Grave.' disease inprison population compared with that in general hospitalpatients. 196 consecutive patient.' (age 13 â€”80) bloodsample. referred to us for thyroid function test. frc@correctional facilities were studied. Assay. of T4(RIA),T3 uptake, Free T4 Ind@ and T3(RIA) were performed. Hyper

thyroidism was confirmed by RAI uptake and scan. 172consecutive age and sex matched hospital patient. servedas control . MAtching was incomplete in patient. youngerthan 17 due to insufficient number of tontrol subject..

Age 16 or less Age 17 or older Grand5. P. Tetel M. P. Total Total

Prisoner..#TFTdone050508957146196#Graves'000841212Hospital

pt.tTPTdone026268957146172IGraves'0 002466

The incidence of Graves' disease was same in the twofeesle group.. It was significantly higher (P < 0.05,Fisher's exact test) in male prisonersolder than 17 yearsthan in the control group.

THE DEFINITION OF ABLATION IN PATIENTS WITh THYROID CANCER:THE EFFECTS OF INSTRUMENTATION AND 1-131 SCAN DOSE. A.Waaman, L. Ramanna, N. Chapman, D. Chapman, M. Brachman, D.Tanasescu, D. Berman, B. Katz, G. Braunstein, Cedars-SinaiMedical Center, Los Angeles, CA

Absence of iodine avid tissue on a diagnostic 1-131 scanhas been generallyacceptedto signify ablation in patientswith thyroid cancer. The purpose of this study is to determine the effect of 1-131 scan dose, scan time and scanning instrumentation on the ability to detect iodine avidtissue.

Twenty-six patients were studied using a 2 and 10 u@i1-131 diagnostic neck and chest scan. Patients were scanned using both a rectilinear scanner CR) and Anger camera(C) with studies performed over a 50 minute period. Datawas acquired on computer in 5 minute increments. The reaults are sununarizedin the followingtables.

2 uCi 2 nCi<2 uCi=2mCi+2mCi10 mCi 10 mCi 10mCi10mCi+10mCi+PATIENTS660311SITES80322

C+R- C.>R C=R [email protected] C-R+2mCi 3 3 3 0 0

lOmCi 1 7 2 0 0

We conclude that the Anger camera neck/chest studies aresuperior to those performed using a 5 inch rectilinearscanner. In addition, the 2 mCi scan dose was inadequateon either instrument in detecting residual sites of iodineavid tissue. The 10 mCi 1-131 scan and a 30-50 minuteAnger camera image showed a significant increase in sensitivity when compared with other dose-instrument-time coinbinations.

EVALUATION OF LOW (29.9 mCi) VS. HIGH DOSE (100 mCi) 1-131THERAPY IN THYROID CARCINOMA PATIENTS . L . Raman, A. Waxman, N. Senael, M. Brachman, D. Tanaaescu, D. Berman and G.Braunstein, Cedars-Sinai Medical Center, Los Angeles, CA.

In an attempt to limit hospitalization and reduce radiation exposure, low dose 1-131 therapy has been suggested asan alternative to high dose treatment regimens in patients(pta.) with differentiated thyroid cancer (DTC). The purpose of this study is to compare the results in pta. withDTC treated concurrently with 29.9 mCi and 100 mCi 1-131regimens.

A total of 26 pta. were studied. 29.9 mCi 1-131 was giyen to 15 and 100 mCi doses to 11. The pta. received therapy 4 to 8 weeks following thyroidectomy. Follow-up scanswere obtained in approximately 6 months using an endogenousTSH stimulation protocol. Ablation (abl.) was evaluatedcomparing 1â€”131neck and chest scans done after surgery andfollowing 1-131 treatment. Both 2 mCi and 10 mCi 1-131scans were done when possible.

The following table summarizes the results.1-131 Dose N of Pta Abl or near Abl Mean 1-131 Dose

29.9 mCi 15 4 37.5100 mCi 11 8 220.0After a single treatment 4 of 15 with 29.9 mCi showed

significant improvement from baseline scans. This subsetof the low dose group went on to ablation or near ablationwith less than 100 mCi 1â€”131.The remaining 11 patients in

C-R55




%1.0.OrqanPeak>10%serum

liversmall bowelurinary bladder0

15120

N/A>T%kidneys60<1%brain,

eye,muscle,bone,lung N/Aheart, stomach. spleen

I'RO(FLI)INGS 01: TIll 28th ANNUAl. MEETING

the low dose group have or will require greater than 100mCi for ablation. No pta. in the low dose group showedprogression.

We conclude that low dose 1-131 therapy may be warrantedas the initial treatment regimen in pta. with DTC. Thepoorly responsive pta. as determined by follow-up scan,should be treated by high regimens.

GASTROENTEROLOGY

BIODISTRIBUTION,DOSIMETRY,TOXICITYOF A NEW HEPATOCYTEAGENT: Tc-99m NEOGALACTOALBUMIN(NGA). R.C. Stadalnik,D.R.Vera,Universityof CaliforniaDavisMedicalCenter,Sacramento,CA.

Previousreportshaveattestedto thepotentialclinicalusefulnessof Tc-9@nNGA,a synthetic ligand that onlybinds to receptors found on hepatocyte membranes,with subsequentdegradationby lysosomalcatabolismandurinaryexcretion.Investigationswereperformedto evaluateitssafety anddosimetry.

Acute toxicity studies in the mousewere performed using20 and44 galactose/albtsuinin 700and5000Xscaledhumandose respectively. No ill effects were observed over a 1-3day period.

Biodistributionstudiesin themouseusing28 galactose/albumin showed the following:

GASTRIC @4PTYINGIN PATIENTS WITH SCLERODERNA. R. Hawkins,N. Anselmo, B. Zamost, J. Hirschberg, P.J. Clsuents, D.E.Furst, L.R. Bennett. UCLASchool of Medicine, Los Angeles,CA.

The effects of scleroderma upon the esophagus and smallbowel are well known; it was our purpose to investigategastric function in this condition. Utilizing a physiologic meal (chicken salad sandwich and 8 oz low fat milk,labelled with 1.0 @iTcâ€”99mâ€”sulfurcolloid), 5 normalsubjects and 18 scleroderma patients were imaged uprightin the anterior and posterior positions at 15 minute intervals for 90 minutes. All subjectsrenamed upright betweenimages. Data was collected on a PDP 11/40 computer, andthe relative amotmt of activity renaming within the stomach was determined using appropriate regions of interestconstructed on the video display. To compensate for attennuation, the geometric mean of the anterior and posteriorvalues were calculated. Normalizing the intial value attime zero to 100%, the relative amount renaming within thestomach as a function of time was determined.

!t2@ X Ia@otopeReMiningin Stcsach(X(s.d.)30mm 45mm 60mm 75mm 90mm

Normal (na5) 73(13) 60(16) 45(23) 32(19) 25(20)Scleroderma (nl8) 90(11) 83(13) 74(14) 70(15) 60(20)

By 30 minutes, the relative amount renaming within thestomach was significantly greater in the scleroderma groupthan the normal group (p <.01 at 30 minutes, p <.005 at 45â€”90 minutes) . We conclude that gastric euptying is significantly delayed in scleroderma; further studies on theeffects of metoclopramide in this condition are beingperformed,

SENSITIVITYOFTECHNETIUM-9@nHIDALIVERSCINTIGRAPHYFORDIAGNOSINGHEPATOMA. S.H. Yeh, S.J. Wang, and L.S. Chu.Veterans General Hospital, Taipei, Taiwan.

Concentrationof Tc-99m PG has been recentlyreported ina caseof hepatoma,suggestingthepossibleroleof biliaryscanningas a meansof increasingthespecificityfordiagnosingsucha tumor(JMud Med21:747-749,1980).Thisled us to performa prospectivestudy with Tc-99m HIDA todetermine its sensitivityin diagnosinghepatoma.

Thestudieswareperformedas follows:Forty-eighthrafterTc-99msulfurcolloidliverscintigraphyforlocalizingintrahepaticmasses,sequentialliverscintiphotoswererecordedafterI.V.injectionof Tc-9@nHIDAon Polaroidfilms at 15-mm intervalsfor one hr. AdditionalGa-67liverscanningwasperformed,if necessary.

Eightypatientsstronglysuspiciousof hepatomain dinicalsituationswerestudied.Thecolloidscandemonstrated focal defects in all of them. The sequentialbiliaryscintiphotosrevealedpersistentvisualizationof hepaticmasses only in 3 of 80 patients. Sensitivity for diagnosisof hepatomawasabout4%. Nonvisualizationoccurredin 77patients.Thediagnosisof hepatomain all80 patientswasconfirmedby laparotomy,biopsy,excision,or postmortemexamination.

Sincethesensitivityof diagnosinghepatomawithTc-99mHIDAisonlyaround4%,we concludethatbiliaryscanningis not worthwhileevenin the selected patients in thecountrieswheretheprevalenceof hepatomaishigh.

RELIABILITY OF Tc-99m PIPIDA HEPATOBILIARYSCINTIGRAPHYFORTHE DIAGNOSES OF TOTAL EXTRAHEPATIC BILIABY OBSTRUCTION.R. Egbert, K.P. Lyons, and B. Felsher, VAMC, Long Beach, CA.

The ability to distinquish total extrahepatic biliaryobstruction (OBST) from severe hepatocellular disease (HCD)is an important aspect of hepatobiliary scintigraphy. Mostagents fail in this regard when the bilirubin rises above10 mg%. In a retrospective analysis of our first 21 monthsusing Tcâ€”99mparaâ€”isopropyliminodiacetic acid, 190 consecutive cases were reviewed. The criteria for OBST wasabsent gallbladder, ductal , and intestinal activity for 18to 2@ hours. The true diagnosis was based on three typesof evidence. â€œAâ€•evidence consisted of autopsy, 1aparoton@r,transhepatic cholangiography, or retrograde cholangiographyâ€œBâ€•evidence was a clinical picture supported by liver bioPay, ultrasound or CT scan. Group â€œCâ€•was nondefinitive or


Dosimetry (mrads/nCi) based on above mouse b@od1stributionandpreviousrabbitblodistributiondatawascalculatedusingMIRD'Sequationsandtables:wholebody(20),bonemarrow(20),liver(60),testis(20),ovaries(75),kidneys(20),bladderwall(600).The latterdosecanbe significantlyreducedby frequentvoiding.Thedosimetryiswithin acceptableand reasonablelimits.

Tc-99mNGA,as a potential hepatocyte imaging agent, demonstrateslowtoxicityanddosimetrywhicharenecessaryfora clinicallyacceptableradiophanmceutical.

UTILITY OF FUNCTIONAL HEPATOBILIARY MARKERS OF Tc-99mPIPIDA AND SULFUR COLLOID IN THE MANAGEMENTOF PATIENTSWITh BIOCHEMICALD$OLESTASIS. E.A. George, S.N. Joshi,R.P. Perrillo, J.W. Fletcher. VA Medical Center andSt. Louis and WashingtonUniversitySchools of Medicine,St. Louis, MO

Five PIPIDA indices,% heart pool clearance (HPcl),Sliver parenchymel reserve (LPre), â€”uptake(LPup), â€”clearance (LPcI),S comon bile duct clearance (@BDcl)and portal hepatic extractionof 5 sulfur colloid,Pâ€”SC,(J NucIMed & AlliedSd 21:107â€”112,1977)werecalculatedby relative temporal quantitation from time activity curves of60 mm PIPIDA and 2 mm of sulfur coilold kinetics. Elevennormal volunteers and 35 patients with cholestasis wereentered in the study; latterconsistedof 16 patientswithcommon bile duct obstructions (CBD0)of which 4 were reexamined post decompression;8 with liverparenchymaldisease(LPD),7 with acute viral hepatitis (AVH)and 12 examinedduring convalescencefrom viral hepatitis (CVH). PIPIDAgroup mean indexvalues and normal range Pâ€”SCdifferedsignificantly between normal subjects and cholestatic patients. Differential diagnosis between intraâ€”and extrahepatic cholestasiswas establishedby the values of PIPIDA@BDcland Pâ€”SC(p<.OO1). In contrast,scintigraphicevalustion of hepatobiliary transit of PIPIDA displayed at5 mmsequentialframesfor 60mmwasaccuratein 25%ofc:soo,75%ofLPDandin71%ofAVH. Repeatexaminationofpatientspost decompressionof CBDO demonstratednormalizetion of all Indices;patients in CVH demonstratedvaryingdegreestowardsnormalizationof indicescorrelatingwellwith the clinical and biochemical status of recovery.



IROCEEDINGS @j:Till 28th ANNUAl. MFITING

lost to follow-up through death or transfer. Twenty patients fit the acintigraphic pattern of OBST. Of thesepatients, 3 were Group C leaving 17 knowns, he of whom hadobstruction (10 Group A and 1@Group B). Two false positivepatients had acute cholecyatltis with cholelithiasis butnormal operative cholangiograns @4and 7 days after scintigraphy. Both patients clinically passed a stone beforesurgery with the bilirubin peaking at 5â€”7mg% at the timeof acintigraphy. The third false positive had essentiallyno concentration of radiotracer in the liver and died withportal vein thrombosis.

In the remaining 170 cases, 127 were Group A & B andnone had OBST. Thirty-five had moderate to severe HCD withan average bilirubin of 9.6 mg% (range 1.2 to 33).

We conclude that with the paraâ€”isopropylderivative OBSTcan be differentiated from HG!) with high sensitivity andgood specificity even with high bilirubin levels using theabove criteria.

12@@ AND@ Br-cz-METHYLTYROSINE

FOR TOMOGRAPHIC PANCREAS IMAGINGF. Ritzl5, G. Kloster**, U.N. Coenen**, U. Tialjar**,G. Stdcklin555Klinikum Barmen and 55lnstitut fÃ¼rChemie, @TA JOlich, FRG

We have recently demonstrated that L-3-231-cL-inethyltyrosine (IMT) has a high pancreatic specificity in mice[1]. In this paper we present first clinical results. Afterintravenous injection of 10 mCi IMT sequential imaging ofthe epigastrial area was started using a large field monocrystal ga=a camera. A rapid accumulation of radioactivitywas observed in the pancreas and in the kidneys without anyvisualisation of the liver, and imaging of the pancreas waspossible within the first 4 minutes after injection. Thereafter accumulation of the activity in the kidneys maskedthe other structures. Using a seven pinhole collimator thekidneys were eliminated to a great extent in tomographicplanes of the pancreas.

Due to the high activity concentration in the kidneys,it seemed necessary to prepare an analogous compound contaming the positron emitter 7Br (T112 = 98 mm) . Thebiodistribution of L-3-7Br-ct-niethyltyrosine (BMT) infemale NMRI mice was almost equal to that of IMT, althoughthe absolute amounts of activity in pancreas and liver werelower. The pancreas-to-liver ratio was 10.9Â±2.25at 3 mmafter i.v. injection and 9.6Â±1.94at 60 mm. During thistime the absolute liver concentration fell from 3.6Â±0.4%dose/g to 1.30Â±0.03%dose/g. Besides the high pancreas-toliver ratio BMT has the advantage that quantitative tomographic images can be obtained without disturbing influencefrom the kidneys when using positron emission tomography.

[1] u. Tialjar, G. Kloster, F. Ritzl, G. Stdcklin,J.nucl.Med. 20, 973â€”976(1979)

COMPUTER ASSISTED DIAGNOSIS OF LIVER DISEASE. E.A. Eikman,G.A. Mack, V.K. Jam, J.A. Madden, M. Lotz, S.F. Connally,L.E. Tenorio, James A. Haley Veterans Hospital, Tampa, FL.,D.L. Flower, Texas Instruments, Houston, TX., R.C. Meade,VA Hospital, Milwaukee, WI.

Increased liver mass, and patchiness of the radiocolloidimage are difficult for the physician to evaluate subjectively. We devised automatic, computerâ€”assistedmethodsthat aid in measurement and interpretation of these twoimage features. An estimate of liver mass and a textureindex of image patchiness designated T9:D4, are each calculated from a preprocessed gasma camera image of the rightlateral projection of the liver. At the operating point ofliver mass estimate of greater than 2.0 kg or T9:D4 greaterthan 0.54, the specificity was 0.96 and sensitivity 0.5for detection of liver disease in a population of 199 malepatients with independent histologic liver diagnoses andnormal volunteers.

The receiver operating characteristic (ROC) curve forour automatic method showed diagnostic performance comparable to or better than the ROC curves of experienced physician observers tested on a subset of the population.

INDIUM-I I 1 LABELLED WHITE CELLS IN BOWEL DISEASE.A.M. Peters, S.H. Saverymuttu, J.P. Lavender, V.S.

Chadwick, and H.J. Hodgson. Hanunersmith Hospital,London, England.

We have attempted to assess the diagnostic usefulnessof Inâ€”Illwhite cefl scanning with quantitative faecal In111 excretion in patients withbowel disease, White cellswere labelled in dextrose saline with Inâ€”Illchelates ofacetylacetone or 8-h.ydroxyquinoline. Scans were performedat L@and 2k hx@after injection and the faeces collectedfor 1@days for quantitation of Inâ€”lll. In some patients,In-Ill labelled transferrin (TF) was injected. In 1@patients with Crohn's disease, 2 with ulcerative colitis,one with radiation enteritis and one with graft versushost disease, prominent localisation of white cells inbowel was seen on scanning and faecal excretion of Inâ€”Illranged from 7 to 31@%of injecteddose. localisedactivitywas seen at a more distal site in the bowel on the 21+hras compared with the 1@hr scan. In 1@patients with Crohn'sdisease, one with ulcerative colitis, one with graft versun host disease and 11 with irritable bowel syndrome,scans were negative and faecal excretion was less than 2%.In other patients, including 5 with Crohn's disease, lessmarked localisation was seen on scans and faecal excretionranged from 2 to 9%. In general, those patients withinflammatory bowel disease who showed low In-Ill excretionwere thought , on clinical grounds , to have inactive disease. In contrast to white cell excretion, which showed apeak on the first day, TF excretion remained low and relatively constant from day to day. In conclusion, labelledwhite cells may be useful in diagnosis and assessment ofbowel disease.

EFFECT OF CIMETEDINE AND PENTAGASTRIN ONSCINTIGRAPHIC STUDIES OF STOMACH WITH TC-99M-PERTECHNETATE. W.H. Schwesinger, J.D. Straw andT.K. Chaudhuri. University of Texas HealthScience Center and V.A. Hospital, San Antonio,TX.

The effect of cimetidine, a parietal H2receptor blocker, and petagastrin, a parietalagonist on Tc-99m-pertechnetate uptake by thestomach has been studied in order to delineatethe mechanisms of control. Using a gamma cameraand a computer, sequential gastric scintiscanswere obtained in anesthetised mongrel dogs for45 minutes following the intravenous injectionof Tc-99m-pertechnetate. The blood disappearancehalf-time and the computer-integrated count overthe flagged gastric region were evaluated. Datain control animals were compared with data fromdogs pretreated by the injection of specificpharmacological agents. At the end of the studythe stomach was washed repeatedly to quantitatefree radioisotope within the lumen of the stomach. Neither cimetidine nor pentagastrin wereshown to produce any significant effect on totalgastric isotope counts when administered in conventional pharmacologic doses. These findingsare consistent with previous reports suggestingthat the uptake occurs at some site other thanthe parietal cells. They are at variance withother anecdotal reports which show radioisotopeuptake to be altered by cimetidine or pentagastn n.

CHOLESCINTIGRAPHY IN COMMONBILE DUCT (CBD) STONE DETECTION:COMPARISON WITH OPERATIVE CHOLANGIOGRAPHY (OC) L. Ramanna,G. Berci, M. Brachman, D. Tanasescu, D. Berman, and A. Waxman, Cedars-Sinai Medical Center, Los Angeles, CA.

The incidence of CBD atone is reported to be 15% in patients having gallbladder stones. OC is a valuable methodin detection of unsuspected calculi in CBD and some authorities recommend its routine use in all patients havingcholecystectomy. The purpose of this study is to evaluatenoninvasive choleacintigraphy (CS) as a test for detectingCBD stone.

Twentyâ€”sevenpatients underwent CS and OC. Studies wereperformed using 3-8 mCi of Tc-99m pipida. Surgery was donewithin a week in moat of the cases. OC was read as positive for stones in the presence of definite intraluminal




T+Oc+ 5OC2Tâ€”119

PRO(EIl)INGS 01: TIll 28th ANNUAl. ME! TIN(@

filling defect. The CS images were read as negative forCBD stone (T-) if it met two criteria, namely, definite gutactivity by 30 minutes and if gut activity was equal to orgreater than CBS activity at 60 to 90 minutes. The testwas read as positive (T+) if it did not meet the above criteria. The results are given below:

CE emptying in response to meals or sham feeding. Theeffect of so.atostatin similarly was obliterated by siwltaneous infusion of octapeptide of cbolecystokinim.

In conclusion, the technique of cholecystoscintigraphyhas been employed to quantitate the effect of the cephalicand gastric phases of vagal stimulation on the rate of GBemptying. Sham feeding stimulates GB emptying, but mot asstrikingly as a meal. Cholimergic blockade completelyobliterates gallbladder response to meals or sham feedings.These techniques represent a valuable tool for the study ofthe relative con@ributiQns of the hormonal and cholinergicstimuli to gallbladder function.

HEMATOLOGY

FUNCTIONAL HYPOSPLENIA AFTER SPLENIC IRRADIATION FORHODGKIN'SDISEASE.C. Norman Coleman, I.RossMcDougall,Morris 0. Dailey and Henry S. Kaplan, StanfordUniversityMedical Center.

Wehave recently reported a case of fulminant pneumococcal sepsis occurring in a patientwith splenic atrophyfrom irradiationfor Hodgkin'sdisease.l As a result weundertooka study of patientswith Hodgkin'sdisease (19)and Non-Hodgkin'slymphoma (6) who had previouslyreceivedsplenic irradiation. All patientshad splenic functionmeasured using red cell morphologystudied by interferencephase microscopyand 99mTc sulfur colloid liver scan. Forred cell morphology200 cells were counted and the percentagecontainingpitscalculated.Forcontrolstherewere27withnormalspleens,6 patientswithHodgkin'sdisease before staging or treatment and 12 patients withHodgkin'sdisease post splenectomy. Spleen scan was done15 mm. after intravenous injection of 5mCi99fllTcsulfurcolloid. Patientswho had receivedsplenic irradiationhad13Â±8%pitted cells whereas normal controls had 0.9Â±1%(P<O.OO1)patientswith untreatedHodgkin'sdisease hadO.6Â±O.5%(P<O.OO1)and those post splenectomyhad 34Â±12%(P<O.OOl).The greatestdiameterof the spleen in those whohad irradiationwas 6.2Â±1.5cmcomparedwith controls,whoseresultswere 9.7Â±l.8cm(PcO.Ol)or controls from the literature with splenic lengthsof 10Â±1.5cm.

The routine use of staging laparotomyand splenectomyin lymphomahasbeenquestionedand incertainsituationshas been replacedby splenic irradiation.This report showsthat an irradiatedspleen is not normal and may offer nomoreprotectionthanonethatis removed.Dailey,M.O.et al Radiation-inducedsplenicatrophyinpatientswith Hodgkin'sdisease and non-Hodgkin'slymphomaN Eng J Med 302:215, 1980.

Tc-99m LABELED GELFOAN EMBOLI - AN AID TO THERAPEUTIC PARTIAL SPLENIC EMBOLIZATION. A.J Gerlock J.A ClantonM.L Born R.C.MacDonnell Jr and W.C.V Parris,Vanderbilt University Medical Center, Nashville, TN

Partial splenic embolization utilizing Tcâ€”99mlabeledGelfoam has been used in the management of four renal traneplant patients with ismunosuppresive therapy inducedleukopenia. Gelfoam emboli were labeled with Tcâ€”99mbystannous reduction utilizing readily available stannouspyrophosphate as the reductant. Each of the labeled partides underwent an antibotic presoak before injection.

During the course of therapy, the arrival of the Gelfoaxrparticles in the spleen were monitored on the persistancescope of the ga@a camera for immediate determination ofemboli localization and polaroid pictures taken for documentation. The gasma camera was also used for whole bodyscanning after the procedure to locate possible ectopicemboli. Selective splenic arteriography was performedprior and post therapy as well as Tcâ€”99mSulfur Colloidscans made 48 hours prior and post therapy to determinethe quantity of splenic tissue embolized during the procedure.

After evaluation, the gasma .amera images of the Tcâ€”99mGelfoam particles in the spleen proved as accurate asselective splenic arteriography in determining the amountof spleen embolized, that no ectopic Gelfoam particleswere found elsewhere in thc@body and that Tcâ€”99mlabeledGelfoam particles were a definite aid during thIs therapeutic procedure.

T@ abnormal scan patterns were noted. 1) Slow and/or noexcretion into the biliary ducts (4/6) 2) Good duct visualization but with persistent cBD activity on three hour delay (1/6). Nineteen of 21 patients were OC- , showed promptduct visualization excretion into the GI tract within 30minutes with GI activity@ at 90 minutes.

The sensitivity of CS for CBD stone detection in thisseries is 0.83 (5 of 6), specificity is 0.90 (19 of 21) andaccuracy is 0.88. We conclude that in patientswith acuteor chronic cholecystitis CS may be useful technique in detection of CBD stone.

EARLYDYNAMICS@IVDT@ASIN ANW@TTOUV@ SCTNTIGRAPHTTN THI INV@TIGATI0N OP DIFPUS@ UV@t DTS@A8B

W.R.Ferguson,J.D.LsirdandK.Crsm1@,Ro@a1VictoriaHospital, Belfast, Northern Ireland, UX.

[email protected] analysis of the first 80 sees. of liv.ruptake, following bolus injection of To-'99. tin oolloid,

@.used to investigate diffuse liver dis.s.e. Timeactivity curves drivsd from regions of interest in liverand spl.sm illustrated uptake during the arterial endvenous input phase. The liver uptake curves were analysedby subtracting a simulated hepatio arterial ourve. Theeimulst ed curve @icomputed from the eplenio uptake bynormalizing the observed splertio ourve to the h.patio at apoint during the arterial input phase. The result of thesubtraction @.a curwe which reflected liver upt.ksarising from portal venous inpet. Using the observedliver uptake end the ooisjsated curves5 the relative arterisi end venous oontrib*stions to the liver uptake werecalculated. This gave reproducible figure..

In a r.tro.p.otive stn4y of liver scans on patientsiiithout liver disease it@ noted that there @sa defin-.able range of nos@s1 value. for the relative arterial endvenous oontrib*itioni. This range @aeclearly separatedfrom that obtained from a similar sised group of oirrhotiopatients. It also appeared that the deviation fxvm thenormal range in individuals ens associated with the seves'ity of liver disease.

A further group of patients, on Kethotrexate forpeoriasis, was studied. A n@ber of these patients showeda@oz@al uptake patterns, apparently directly associatedwith reversible liver to@oity.

This technique appear. useful in the diagnosis andmonitoring of diffuse liver disease and, possibly, also ofliver toxicity.

c@JANTITATIVE CHOLECYSTOSCINTIGRAPHT-EFPECTS OF SHAM FEEDINGIN MAN. E.Rock, Z.Rattner, L.S.Malaud, R.S.Fisher. TespleUniversity Hospital and Medical School, Philadelphia, PA.

The mechanisms by which the gallbladder (GB) empties havenot yet been completely elucidated. The purposes of thisstudy were to utilize scimtigraphy to quantitatively determine GB response to a standard liquid meal, a solid mealconsisting of sirloin steak and french fried potatoes andsham feeding of the sane solid meal in order to quamtitatethecephalicandgastriccomponentsof vaga].stimulation.

Thirty normal subjects were studied employing SaiCi (iv)Tcâ€”99mPIPIDA followed 45â€”60mm. by the meal or sham feeding. Images and counts were obtained for 2 hrs at 15minute intervals.

Cs emptying during the first 90 mm. was more rapid withthe liquid meal compared to the solid meal. GB emptyingduring sham feeding was obliterated by simultaneousatropine infusion. Emptying of the CE in response to bothliquid and solid meals was decreased, but not obliteratedby infusion of atropine.

An infusion of soisatostatin, a polypeptide which inhibitsthe release of many gastrointestinal hormones, obliterated




PROCILI)INGS 01: TIll 28th ANNUAL. MIETIN(i

(PVC: 45.1*7.2%, AVC:@.9t9.8X). QlRGlc of higher order AVCirK@reased 2. 5 tImes PVC with increasii@ scene complexity.Stepaise OI@Glc decreases occured as lesion sites in visualpathway soved distally (optic nerve PVC â€”102,AVC â€”12%;tha]smic/optic radiation: PVC â€”19@8. 1%, AVC â€”33. @5.94). Visualhallucinations produced 2 fold increases in visual cortex.

Auditory controls @re same as above except ears wreplugged . Pairs of tone sequei@es wre given sonaurally andsubject required to identify similar pairs. Increases wre fouadin frontal cortex with assysetry to right frontal (6 .2%, p<0.01), posterior tesporal (9..@, p <0.05) and right parietal(5.6%p <0.01)cortexregardlessof ear stimulated. Verbalstimulation presented sonaurally produced increased cortical@WGlc in frontal cortex, left posterior temporal (4.1% p <0.01),AVC (15.1%, p <0.01) and right frontal (7.0%, p <0.025)regardless of side stimulated . Bilateral stimulation with storyplus music produced syssnetric activation of frontoâ€”tesporalregions and leftâ€”sided tenporo-parietal activation. In allauditory stimulation, Heschl's gyri and planua tenporale respondm1 consistently to content rather tban side of input. Thosestudies represent selective cortical activation determined bystimulus content.

QUANTITATIVE IMAGING OF CEREBROSPINAL FLUID (CSF) DYNAMICSIN PATIENTSWITh MENINGEALMETASTASES. D.C. Chen, S.A.Grossman, E.E. Camargo, K.G. Sachariah, D.L. Trump, U.N.Wagner, Jr. The Johns Hopkins Medical Institutions, Baltimore, MD.

We have investigated CSF flow abnormalities in patients (pts) with meningeal metastases (*1). In 17 ptswith various malignancies27 studieswere performed. Sequential images over the head and spine were obtainedimmediately, 4 hrs, 24 hrs and 48 hrs after injection of500 pCi In-lll DTPA into a lateral ventricle through an@bimiayareservoir. In 9 of these pts the images were alsostored on computer for quantification. Regions of interestwere chosen over the lateral ventricle, cisterna magna,cortical convexities, cervical and lumbar spine, and timeactivity curves generated as percent of the initial activity or as counts/pixel. Normal CSF flow was found in 7/17pts. In pts with normal CSF dynamics, the ventricularactivity declined rapidly from 100% of the initial activity to 27% at 4 hrs and 0.5% at 48 hrs. In 10/17 pts 3types of CSF flow abnormalities were recognized. In Type Iabnormality (4 pts) the radiotracer failed to leave the yentricular system. In Type II (4 pts) the spinal canal wasobstructed and delayed ventricular clearance was observed(p<0.05). In Type III (2 pts) asymmetrical tracer concentration over the cortical convexities was noted both visually and quantitatively. Pts with Type I pattern had significantly shorter survival than all other pts (p<O.OS).Quantitative imaging of CSF dynamics with In-lll DTPAafter injection through Oimnayareservoirs in patients withmeningeal inetastases is helpful not only in prognosis, butalso in the assessment of the distribution of injectedchemotherapeutic drugs.

EFFECT OF ISCHEMIAUPON QUANTIFICATIONOF LOCAL CEREBRALMETABOLICRATES FOR GLUCOSE WITH 2-(F-18) FLUORO-DEOXYGLUCOSE (FDG). R. Hawkins,N. Phelps, S. C. Huang, D. Kuhl.UCLA School of Medicine,Los Angeles, CA.

We investigatedthe effects of ischemiaupon the parameters (rate constantsk(l)*, k(2)*, k(3)*, and k(4)* and thelumped constant (LC) used in tomographicmeasurementof local cerebral glucosemetabolism. All terms of LC=(A/@)(Vm*Km/VmKm*),except 4@are ratios and should remain constant. â€¢=(l-k(4)Cm/k(3)Ce)is difficultto evaluate. Itmay be reformulatedto 4,=(l_k(4)*bCm/k(3)*aCe)where b anda are ratios of Michaelis Mentenparameters that should remain constant,and Cm and Ce are the steady state tissueconcentrationsof FDG and FDG-6 phosphate. Because k(3)*and k(4)* can be measured and the Cm/Ce ratio can be inferred from animal data, the stabilityof 4 and LC can be estimated. With values for b and a obtained from the literature, 4 can be numericallyevaluated. Rate constants inischemicand non-ischemicregionswere generatedin six patients with strokes. Patients were divided into groups ofthree based upon the degree of ischemia. In group I, theaverage relativeLCMRG1c in ischemicregions compared tocontralalateraltissue was 0.40 * 0.14, while in group II

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MISCELLANEOUS

REGIONAL TRENDS IN NUCLEAR MEDICINE UTILIZATION IN NORThERNCALIFORNIA. D.C. Price, P. Matin, R.P. Carretta,R.W. Myers and J.M. Fontius. Northern California Chapter,Society of Nuclear Medicine, San Francisco, CA

In order to evaluate Nuclear Medicine utilization overthe 5â€”yearperiod 1975â€”1979,a 2â€”pagequestionnaire wassent to all 142 Northern California hospitals requestingannual procedure data by test, and responses to severalrelated questions. Of the 69 responders, 47 provided suffâ€”icient data to analyse numerical trends for the 12,179 hoepital beds represented. Total procedures increased 4.3%in 1976, decreased 1.1% and 4.1% in 1977 and 1978, and thenincreased 0.6% in 1979 for an overall average annual dcclinc of 0.1%. In the 3 university hospitals of the region,the annual decline averaged 4.2%, although utilization perbed began at a higher level (9.3) than in community hospitals (8.0). For all responders, the greatest 5â€”yeardcclinc occurred in brain scans (57.4%), followed by renal(13.1%), liverâ€”spleen(8.2%), lung (7.7%) and thyroid(6.6%). During this period, cardiovascular studies grew360.1%, gallbladder function 297.5%, Galliumâ€”67procedures236.1%, bone scans 44.2% and â€œotherâ€•76.6%. In the 14hospitals demonstrating significant growth, no specificassociated factors could be identified other than goodreferring physician rapport and regular participation inother department rounds and seminars. In 74% of the reaponders there was interest in having centrallyâ€”supportedand organized GfE speakers available.

NEUROLOGY

QUANTITATIVE EVALUATION OF CEREBROSPINAL FLUID SHUNT FLOW.S. Chervu, L.R. Chervu, B. Vallabhajosyula, K.M. Shapiro,D.M. Milstein, K. Shulman, and M.D. Blaufox. AlbertEinstein College of Medicine, Bronx, NY.

Evaluation of shunt flow in patients with a surgicalshunt for obstructive hydrocephalus is important to assesschanges in clinical status. A rigorous method for quantifying cerebroapinal fluid (CSF) flow in prosthetic shuntsystems has been developed for this purpose. Clearance ofradioactivity for several calibrated flow rates using aHarvard infusion pump was determined by injecting theRickham reservoir of a R.ickhamâ€”Holtervalve system with100 @iCiof Tcâ€”99mpertechnetate. Flow rates plottedagainst respective mean clearances yielded a correlationcoefficient of 0.99. Use of either elliptical or cylindrical Holter valves with the Rickham reservoir yielded 2different regression lines even though the valves wereshielded and only the clearance of the injected Rickhamwas measured. These regression lines were used to determine in vivo flow from clearances calculated after injecting the Rickham reservoir of the patient. The uniqueclearance characteristic of the individual shunt systemrequires that calibration curves be derived from theentire shunt system and not just the injected chamber,identical to the patient system. In 3 patients in whomthere was no clearance, obstruction of shunt was confirmedat surgery. In the remaining 5 patients there was excellent correlation between the clinical status and the shuntflow rates determined in vivo from the clearance and the invitro calibration curve. The excellent correlation between flow rates and the clinical findings supports thereliability of in vivo isotope clearances for evaluationof CSF shunt flow.

MEEABOLICRESPO@GEOF TUE &tAIN TO VISUAL AND AUDITORYSTIMULknON AM@E@PRIVATION:STUDIESWITh @SITW@1CQ@[email protected]. Phelps, J.C. Mazziotta, J. Engel Jr., D.E. Kuhl. UQASchool of Medicine, Los Angeles, CA.

Studies wre performed in pairs; controls had eyes patched,minimal sours! aed no movei@nt . Increasit@ cerebral metabolicrate for glucose (QVG1c) of primery (PVC) aed associative (AVC)visual cortmc occured as stimulus complexity increased from whitelight (PVC: [email protected]%, AVC: 6.1 Â±2.8%) to checkerboard patternwith sonocuiar (PVC: 17.4*3.3%, AVC: 21.9Â±4.9%) or binocular(PVC: 27.616.@, AVC: 26.7Â±9.3%) vision aed complex outdoor scene

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I'KoFIDIN;S 01 FIlE 2@fthANNtJAI. MIIâ€¢TIN(;


the value was 0.74 * 0.05. The average relativechange ink(4)*/k(3)*(definedast@k(4)*/k(3)*)from normal to ischemictissue in group I was 2.64 * 0.58, and @roupII was 0.98 *0.22. 4 was approximately0.99 in non-ischemictissue andgroup II ischemic tissue, and was 0.95 in group I ischemictissue. This producedan increaseof approximately4% inLC in group I, and no change in LC in group II. Averagesets of rate constants for ischemic tissue improved bothtemporalstabilityand accuracyof values of LCMRG1c cornpared to results obtainedwith rate constantsfrom normaladults.

POSITRON EMISSION TOMOGRAPHYOF F-l8 LABELLED LOWERFLUOROALKANES IN THE BRAIN. J.E. Holden, S.J. Gatley,and R.E. Polcyn. Department of Radiology, University ofWisconsin Clinical Science Center and Nuclear MedicineService, William S. Middleton V.A. Hospital, Madison, WI.

We report the progress of our developa@ent of the lowerfluoroalkanes (methyl, ethyl, isopropyl, n-propylfluoride) as neurological probes in conjunction with positron emission tomography performed on the ORTEC ECAT IItomograph at the Middleton V.A. Hospital. These agentswere determined to be inert in vivo, and measured wholeblood Ostwald solubility coefficients ranged from 1.05 to1.2 (1). Tissuespecificactivitiessufficientfordynamictomographic imaging can be attained from rapid inhalationadministration of 5-10 mCi of these agents, and a methodhas been developed for deriving both blood flow and volumeof distribution from their cerebral kinetics on a pixel-bypixel basis. The aqueous solubility coefficients of thesefour agents are all very similar;however, their Ostwaldsolubility coefficients in paraffin oil range from 1.1 to12.3 (3). Differences in derived regional volumes of distribution from sequential studies with two or more of theseagents thus can provide a sensitive measurement of regional lipid concentration. Successful preliminary validationof this concept has been performed in our laboratory.

1. Gatley SJ, Hichwa RD, Shaughnessy WE, et al: F-l8-labelled lower fluoroalkanes; reactor-produced gaseousphysiological tracers. Int J Appl Radiat Isotopes(in press).

ONCOLOGY

COMPARISONOF SCINTIGRAPHICAND SIALOGRAPHICDIAGNOSTICMEThODSFORFUNCTIONALAND STRUCTURALCHANGESIN SALIVARYGLANDS: L.D. Samuels,A. Markitzlu,J. Harnik andJ. Shani,HadassaUniversityHospital,Jerusalem,Israel.

A seriesof 35 patientswithcomplaintsof xerostomlahavebeen investigated by dynamic quantitative scintigraphicstudiesof parotid and submandibulargland functionandslalography,to compare the two diagnosticmethods. Contrast sialographywas performedby standardmethods. Scmtigraphicstudieswere performedwith patients facing ahigh-resolution,parallel-holecollimatorcenteredon thechin with submandibularand parotid glands approximatelyequidistant from camera. Ic 99m pertechnetate, 3-5mCi, wasinjected IV and forty one-minute images were acquired andcomputer-stored. After thirtyminutes lemonwas given p.o.to stimulatedischarge. ROl over salivaryglands, oral cavity and orbit were identified and curves of uptake and cxcretionwere computer-plotted.Sevencategoriesof salivarypathologyhave been studied. (1) congenitalmalformations(2) SJogren's syndrome (3) radiation damage (4) drug-induced dysfunction(5) sialadenosis(6) sialadenitisand (7)other diseases. We find scintigraphysuperiorto sialography in providingsimultaneousfunctionstudiesof allfour salivaryglands and for its freedom from any sideeffects.Indrug-inducedsalivarydiseasesialographicstudiesarenormalwhereasscintigraphicstudiesrevealfunctionalimpairment,whose improvementcan be seen in followup studies. In congenitalsalivarydefects the two procedures are complimentary,while in recurrentsialadenitisand in sialadenosissialographyshows the ductal pathologybetterthanscintigraphy.inSjogren'ssyndromeandwithradiation damage and parenchymaldisease scintigraphicstudies are superior to sialography in showing parenchymalfunction.

PEDIATRICS

LUNG SCINTICRAPHY IN PRIMARY LUNG TUBERCULOSIS INCHILDREN. J.Vandevivere, A.Malfroot, C.Bogaert, I.Dab,M.Spehl, M.Toppet and A.Piepsz. St.Peter's hospital,Free University of Brussels, Belgium.

Early recognition of bronchial obstruction is mandatoryin order to prevent bronchial lesion in primary lungtuberculosis. The aim of the present study was toevaluate the contribution of Tcâ€”99mMAA perfusion andKr-81m ventilation lung scintigraphy for the detection ofsevere bronchial obstruction. In a first series of 47patients who underwent bronchoscopy on the basis ofX-ray data (consolidation or lymph nodes),17 severeobstructions were detected. Among them,l4 were associatedwith chest Xâ€”rayconsolidation (sensitivity : 827.),whilein the remaining 3, only lymph nodes were observed.Lung scintigraphy was performed in all these 47 patientsinitially suspected of having bronchial obstruction. Theassociation of a striking scintigraphic defect with aradiological consolidation allowed the recognition of 16of the 17 severe obstructions, giving a sensitivity of947..The specificity however was 337.,X-ray consolidationas well as scintigraphic lesion being often observed inthe absence of any significant obstruction. In a secondseries of 30 children with tuberculin conversion, bothscintigraphy and chest X-ray were systematically performed.Lesions were shown in 11 children with both methods. In 1child, consolidation was noted on X-ray without corresponding scintigraphic defect, on the other hand 3children had a striking scintigraphic defect with anormal chest Xâ€”ray.It is suggested that lung scintigraphymay be contributivein the decisionof bronchoscopyinchildren with primary lung tuberculosis.

il-IE VALUEOF RADIcWCLIDE BRAIN FLO@AND STATIC S@flJDIESINThE DETERMINATIONOF CEREBRALDEATh IN cHILDREN. G.N. Sfakianakis, B. Hoizeun, R.G. Curlers, J.E. @â€˜bntesand C. Ajinone-Marsan. Ihiversity of Miami, Miami, FL

Lack of children included in the cooperative cerbraldeath study, need for transplant organs, effect of barbiturate therapy on the electroencephalogram (EEG), psychologicand economic factors, require the establishment of a definitive method for the earlier and unqt@stionable diagnosisof cerebral death, which up to this time relies on two successive isoelectric EEGs. In the past ten months 18 childrun who were admitted to the Jackson t4morial Hospital Intensive Care Unit developed neurological examination paramaters of cerebral death. @ieor serial EEG's were obtainednear time of the isotope stislywhich was performed after aniv injection of Tc-99m Glucoheptonate (400 jiCi/kg) with amininurn of 2 aCi. Sequential imaging at 3 second intervalsfor two minutes was followed by a static study acquiring500,000 counts in the anterior projection. Abnormal studiesshowed a) decreased flow but normal superior sagital sinus(SSS)on thestaticimage,b) absentflowbutvisibleSSSand c) No visible neither flow nor SSS. A lack of flow predicted ultimate death in all 10 patients (13 studies). Infour patients serial scans showed a gradual reduction inflow while the EEG's failed to detect cerebral activity. Inall patients with timely comparative tests (EEG, Angiograin,contrast transmission tomography) radionuclide study wasthe last to show lack of cerebral blood flow signifyingcerebral death. Ã§kiestionableEEG results could be clarifiedby a flow study, because barbiturate treatment did not affect cerebral blood fics:. @*ithe basis of this preliminarydata it is felt that this test provides more definitivediagnosis of cerebral death in children, indicating a lackof necessity for a follow-up EEG at 24 hours.

POSTOPERATIVE EVALUATION OF COMPLICATIONS OF THE FONTANPROCEDURE BY RADIONUCLIDE ANGIOGRAPHY. M.J. Gelfand, G.G.Janos, D.C. Schwartz, S. Kaplan. E.L. Saenger RadioisotopeLaboratory and Division of Pediatric Cardiology, Children'sHospital and University of Cincinnati, Cincinnati, OH.

Immediate and longâ€”termcomplications of the Fontanprocedure (right atrium-pulmonary artery conduit and atrial



PROCEEDINGS OF THE 28th ANNUAl. MEETING

aeptal defect closure for tricuspid atresia) include:varying degrees of obstruction to pulmonary artery flow,rightâ€”toâ€”left (Râ€”L) interatrial or interpulmonary shuntand systemic venous hypertension from right atrial (RA)failure, Following the Fontan procedure, 5 patients (ages8-17) were evaluated using firstâ€”pass and gated radionuclide angiography (RNA).

Two patients had postâ€”operativeheart failure due to RAoutflow obstruction. In both cases, the site of obstruction was evident on firstâ€”passRNA. One had obstruction ofthe proximal end of the conduit by pannus at re-operation.Gated RA ejection fraction (EF) was 0,15 before and 0.30after reâ€”operation. The other had near complete obatruction of the left pulmonaryartery (LPA)at the site of aprevious Potts anastomosia. Gated RA EF was 0.19 beforeand 0@22 after unsuccessful LPA reconstruction, A smallR-L interatrial shunt was also noted in this patient byfirst-pass RNA; Tc-99mâ€”macroaggregated albumin imagingconfirmed the Râ€”Lshunt and also the anticipated asymmetryof lung perfusion. Gated RA EF was 0.25, 0.31 and 0.51in the 3 patients without RA outflow obstruction. Gatedleft ventricular (LV) EF ranged from 0.33 to 0.73. Abnormel LV EF occurred only in the cases with RA outflow obatruction.

RNA is valuable in the detection of complications afterthe Fontan procedure. Quantitation of RA EF is possiblein these patients with hypoplastic right ventricles.

DIAGNOSISOF BILIARY ATRESIA WITH HEPATOBILIARYIMAGING.J.P. Gerhold, W.C. Klingensmith III, C.C. Kuni, J.R.Lilly, A. Silverman, A. R. Fritzberg, and T. Nixt, University of Colorado Health SciencesCenter, Denver, CO.

Early and accuratedifferentiationof biliary atresia(BA) from other causes of neonatal jaundice is important.Patients with BA may benefit from surgery and a Kasaiprocedure if secondary hepatocyte damage is not severe;patients with other causes of neonatal jaundice, e.g.neonatal hepatitis (NH), should not undergo surgery.Fourteen patients with BA and 6 patients with NH (noother causes of neonatal jaundice were encountered) werestudied preoperativelywith either Tc-99m-diethyl-IDAorTc-99rn-diisopropyl-IDA.Imaging began at 5 mm and wascontinued until intestinal activity was seen or until 24hr. Two parameters were evaluated: 1) hepatocyteclearance (liverto backgroundratio at 5 mm; visuallygraded1 to 4 by two observers, 1= normal) and 2) time ofintestinal activity. The 14 patients with BA had hepatocyte clearances of 1.7 Â±0.5 (meanÂ±S.D.); intestinalactivity was never seen through 24 hours. One of twoobservers categorized 1 of 14 BA patients as indeterminate; all other determinationsin BA atresia patientswere correct. The 6 patients with NH had hepatocyteclearances of of 1.6 Â± 0.7 (mean Â±S.D.); intestinalactivity was seen by 24 hr in 5. The NH patientwithoutintestinal activity through 24 hrs was miscategorizedasBA by both observeres; the other 5 were categorizedcorrectly as not having BA. Sensitivity and specificityof hepatobiliary imaging for BA were 96% and 83,%respectively;overall accuracy was 93%. Although severalquestions remain unanswered, hepatobiliary imaging appears promisingfor the noninvasivediagnosisof BA.

PERIPHERAL VASCULAR

EFFECT OF EXTERNAL PNEUMATIC COMPRESSION ONVENOUS VOLUMES OF THE CALF.@K*m@@ @hapi@e@K.@A M@Iusick@ H.,.L@ Strailas.Massachusetts General Hospital and MassachusettsInstitute of Technology, Boston, MA.

External pneumatic compression has beensuggested as a means of reducing the iiicidenceof deep venous thrombophlebitis@in patients atprolonged bed rest. The effectiveness of thistechnique is related to both the amount and rateof venous emptying caused by the compressiondevice. To determine whether a single or gradedcompression cycle of an external pneumaticcompression device caused greater changes invenous volume, multigatÃ§d blood pool scans wererecorded synchronized with the cuff compressioncycle. Images were accumulated for 0.5seconds/frame for 32 frames over 30 cycles.Data were @nalyzed by placing aregion-of-interest over the vessels of the calf,

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and measuring the activity at each time point inthe average cycle. The results were expressedas percent change from the beginning of thecompression cycle to that at thenadir of thecurve, divided by the peak activity. Twocompression cycles were analyzed: the first wasgraded pressure with 6OmmHg at the knees, andinflated simultaneously. In the secondanalysis, the cuffs were inflated sequentiallyfrom the ankle to the knee. Both cycles resultin approximately a 40% decrease of v9lume with amean difference between the two studies of 4.6%with a standard deviation of 2.5. (T3.72 at 4degrees of freedom).

These data indicate that although there isonly a small difference in the amount of bloodvolume caused by graded sequential oversimultaneous cuff inflation, both techniquesprovide marked reduction in the resting bloodvolume. This technique also provides a means ofdirectly imaging and measuring blood volumechanges.

EFFECT OF TIMING ON VISIBILITY OF BYPASSGRAFTS IMAGED WITH IN-lil-OXINE-LABELEDPLATELETS. .L@T Christenso@@. J@@[email protected]@G..L L'Itjligp KC._RanaI@@ SXi@[email protected] [email protected]@. Massachusetts GeneralHospital, Boston, MA.

The ability to image arterial bypass grafts withIn-11l-oxine-labeled platelets may depend on thetiming betw?en exposure of a graft to blood(declamping@ and the injection of labeled platelets.To study this timing, PTFE grafts were implanted inthe carotid and femoral arteries in each of 6 dogs.Grafts were declamped at one hour intervals (sequence1-4. respectively) and labeled platelets were injectedjust prior to declamping graft 4. In 3 dogs, grafts 1and 2 were implanted into the carotidarteries, andgrafts 3 and 4 into the femoral arteries;thisprotocol was rÃ§versed in the remaining dogs. On theaverage, labeling efficiency was 72%, O.6dmCi activitywas injÃ§cted, and label was depleted from the dog'sblood with a half-life of 32.1 hrs. In allpreparations, satisfactory aggregation of labeledplatelets was recÃ§rded. Activity in each graft (A@analyzed from digital nuclear images, with correctionsfor soft tissue and blood pool background@ wasmeasured daily for 5 days. Values were highlyconsistent when grafts were grouped by sequencenumber, but not by locatio9. Significantly differentpatterns of activity vs. time were obtained betweengrafts 1-2 and grafts 3-4. Grafts 3 and 4 werevisible immediately (A 3.3 + 0.3 and5.2 Â±0.3,respectively; mean Â±SEM), ana activities decreased by70% on day 5. Grafts 1 and 2 were generally notvisible on day 1, but became as visible as graft 3 byday 5. Thus, if labeled platelets are injected morethan 1 hr after declamping a PTFE bypass graft, aminimum of 3 days is required before such grafts arevisible by gamma imaging.

SKIN PERFUSION: NORMAL RANGE AND THE EFFECTS OF AMBIENTTEMPERaTURE. R.E. Henry, M.J. Daly and J.H. Hughes. VAMedical Center and University of Arizona, Tucson, Arizona.

We previously reported a technique for determining skincapillary perfusion and its use in ischemlc limb disease(JNM 21:156, 1980). This report details the effects of ambient temperature and establishes the normal range for men.

Skin perfusion was determined in 50 healthy Caucasianmale volunteers, age 20â€”45,below the knee (BK) and overthe ankle (Symes) with duplicate injections of 0.05 mlXeâ€”133in saline (100â€”300uCi).The washout of Xeâ€”133wasmeasured with a gamma cameraâ€”computersystem and enteredinto the Schmidt Kety equation. After a 15 nm. equilibration period, each subject was examined at 250 and,on asecond visit, at 200, 300, or 35Â°Cambient temperature.

At 25Â°,perfusion at the BK level was 6.8Â±2.0ml/min/100gm (mean Â±SD) with a range of 2.8-10.8. Perfusion at theSynes level was 6.6Â±2.2with a range of 2.2-11.8. Ambienttemperature had a pronounced effect on akin perfusion. At30Â°Cperfusion was 7.0Â±0.4 (mean Â±SE) at the Symes site,only slightly higher than at 25Â°C. At 35Â°,however, it was10.4Â±0.8and at 200 it was 3.7Â±0.5reflecting vasodilationor vasoconstriction, respectively, in response to ambienttemperature. Moreover, serial measurements demonstratedthat at 200 and 350 perfusion continued to fall or rise,respectively.

Knowledge of the normal range is important in theclinical use of skin perfusion measurements. The markedvariation in response to room temperature indicates theneed to perform the test in a comfortably warm (25â€”30Â°C)environment to produce reproducible and comparable results.

Furthermore, an equilibrium of at least 15 mm. isnecessary before beginning the test to allow the patient'sskin perfusion to stabilize.



PROCEIi)IN(iS OF THE 28th ANNUAL MEETING

inspired concentration and plotted against ventilation/unitvolume. A linear relationship was evident up to about 7(L/min)/L (correlation coefficientâ€”O.91). This is greaterthan that predicted by the widely used theoretical wellmixed single compartment model and greater than thatmeasured in a single compartment physical model. Analysisof the gated data showed that the maximum/minimum countratio over the entire lung was independent of ventilation oracquisition view and was larger than expected from the knowntidal volume and FRC. Estimation of FRC using this ratioyielded a mean value of 60.9 Â±9.4 (SD)% of the measuredFRC. We interpret this to mean that mixing of the isotopewith the resident lung gas is incomplete. This does notinvalidate Kr use for clinical imaging but indicates thatits distribution may be to a smaller volume than expected.It also suggests that Kr may provide a nonâ€”invasivemeans ofestimating the degree of gas mixing in intact lungs.(supported in part by AFOSR contract #F49620â€”78â€”Câ€”0058)

SCINTIGRAPHIC DETERMINATION OF PUlMONARY EMDOLISM: THEVATJJE OF AEROSOL IN INDETERMINATE STUDIES . L. Ramann, A.Waxman, N. Brachman, P. Julien, D. Berman, D. Tanasescu,S. Koerner. Cedarsâ€”SinaiMedical Center, Los Angeles, CA

The advantages of aerosol inhalation lung scintigraphyover xenon inhalation and washout studies are the improvedresolution and precise comparison with perfusion images inmultiple projections. This study was done to see if theaerosol study increased the diagnostic efficacy of lungscintigraphy in patients who were categorized as indeterminate following a conventional ventilation/perfusion study.

Twenty patients with suspected pulmonary embolism underwent xenon ventilation (V), [email protected] (P), and Tc99m aerosol (Aero) acintigraphy and pulmonary angiography(PA) within 48 hours of onset of symptoms. Eleven of the20 patients in this study were defined as having a high indeterminate (HI) study when the posterior P was normal andother views abnormal if the posterior V was also normal.Indeterminate (I) studies demonstrated matching V and P abnormalities. Patients were assigned a probability beforeand after the Aero study.

Eight of the 11 patients in the HI category were changedto H because of Aero, 5 had emboli on PA, 1 had vaaculitia,2 had a clinical episode consistent with PB but normal PA.Three of the 11 patients in this group were changed to Iwhen the Aero indicated airway disease precisely matching Pdefects present on multiple views. None of these patientshad emboli on PA. In 14 of 20 patients studied, the Aerowas instrumental in assigning a more accurate prcbability.

We conclude that the aerosol technique is important whenP defects are not seen in the posterior projection. In addition, airway disease can often be more precisely delineated on aerosol than xenon because of higher resolution andthe ability to obtain multiple projections.


PULMONARY

BREATHING PATTERNS STUDIED BY DYNAMIC TRANSMISSION SCINTIGRAPHY AND TEMPORALFOURIER TRANSFORM.F. Deconinck,A.Bossuyt,W. Vincken.AZ-VUB, 1090 Brussels,BELGIUM.

In this study we describe the use of amplitude/phase functional images obtained by temporal Fourier transform (iTT)to evaluatethepatternsof regionallungexpansioninhealthy individualsunder differentbreathingconditions(slowabdominalbreathing(SAB),slow upper chest breathing(SUCB)and fast breathing(FB)),andin patientswith chronic obstructivelung disease(COLD)beforeandafter chest physiotherapy by which abdominalbreathing (AB) was instructed.Dynamic lung transmissionscintigraphywas performedto obtame a time series of images in which temporalchanges incount rate principallyreflect the changes in lung expansionduring respiration. In healthy non smokers, SAB is characterizedby a minimum amplitudeat the lung bases and a phaseshift between the upper lobe and the base, the top expanding later.Under SUCB the amplitude image is more uniformly distributedbut expansionstill predominatesat thelungbases. The phase shift between upper and lower lobes disappearsormayevenbeinverted.FBhasa predominantupperchest breathing (UCB) patternwith an even more pronouncedphase inversion.These distinct patternswere not affectedby a standing versus supine position. In COLD patientstheamplitude/phasedistributionduring spontaneousbreathingismarkedlymore heterogeneous,emphysematousbullae beingcharacterizedby a decrease in amplitudeand importantphaseshifts. After physiotherapythe amplitude/phaseimagesshowed increasedlung expansionat the bases, correspondingtoa more pronouncedAS pattern. In conclusion,TFT associatedwith transmission densitography allows to objectivate regional changes in lung expansionrelated to voluntarybreathing manoeuvresas well as to pathologicdisturbances.

LIMITATIONS OF KRYPTON 81â€”MUSE FOR VENTILATION IMAGING.M.M.Graham &H.I.Modell, Depts. Nuc. Med. and Physiol. &Biophys., Univ. Wash., Seattle, WA

Krypton 81m (Kr) is beginning to be used widely as aventilation imaging agent. However, little work has beendone to confirm the validity of its use in quantitatingregional ventilation. Ten dogs were anesthetized withpentobarbital, paralyzed with succinylcholine, andventilated mechanically over a wide range of ventilationrates with a uniform concentration of Kr in the inspiredgas. Activity was recorded with a gamma camera and computeras 1.5â€”2mm. averaged images (anterior view) or as 28cyclic gated images covering the respiratory cycle (anteriorand posterior views). The functional residual capacity(FEC) was measured by indicator dilution with Xeâ€”133. Totallung activity from time averaged images was normalized to



1981;22:P61-P92.J Nucl Med. Abstracts for Poster Sessions

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