Contamination from ‘@‘I,‘°3Ru,and 239Np in the

Eluate of 99Mo.@99mTc Generators Loaded

with (n, y)-Produced 99Mo

M. W. Billinghurstand F.W. Hreczuch

Health Sciences Centre, Winnipeg, Manitoba, Canada

Iodine-131, ruthenium-103, and neptunium.239 are present as contamifonts in the eluate of 99Mo@s9mTc generators loaded with °9Mo prepared by

thermal-neutron irradiation of enriched 98Mo. The elution pattern of eachof these contaminants is determined, together with the amounts found inthe eluate of all generators tested over a 7.month period.

J Nuci Med 17: 840—843,1976

The literature contains a number of reports on theradioactive contaminants found in 99mTc@pertechne@tate. Some are concerned with the o9mTc obtainedby liquid—liquid extraction from the parent 99Mo(1—3),one paper deals with the 99mTcobtained fromcommercial suppliers as “instant―pertechnetate (4),and still others with the o9mTc obtained from commercially available 99Mo@@U9mTcgenerators (3,5—8).These reports may also be classified by notingwhether the parent °°Mowas obtained from fissionproduct material (4,8) or from thermal-neutron irradiation of enriched 98Mo (1,3,5—7).

Iodine-I 31, ruthenium-103, and molybdenum-99are fission products that are difficult to eliminatecompletely. For this reason, ‘@‘Iand ‘°3Rufrequentlycontaminate the onmTc produced from fission-product

99Mo. In recognition of this fact, the atomic energycontrol agencies have specified maximum permissiblelevels of these two contaminants in 99mTcat the timeof injection. However, such contamination has notbeen reported previously for the 99mTc obtained from(n,-y)-produced 99Mo. In this paper we report theconsistent appearance of 131J, ‘°3Ru,and 239Np inthe eluate of commercially available generatorsloaded with (n,y) 99Mo between the end of Februaryand the end of September 1975.

MATERIALS AND METHODS

As part of our routine quality-control program,all ooMo@9omTcgenerators are eluted a final timeon the day the new generators arrive, i.e., on a Mon

day after a week of use. This eluate is stored for1 week and then analyzed with a Ge(Li) detectorcoupled to a 5 12-channel analyzer. In this way weobtain, after the fact, data on any gamma-emitting

impurities present in nanocurie amounts after the99mTc has decayed to about 0. 1 PCi.

All the ftftMo@@.99mTcgenerators used in this studywere New England Nuclear 400- or 500-mCi generators. The 99Mo used in these generators was supplied to New England Nuclear by General Electricand is produced by the (n,y) reaction. Since theliquid—liquid extraction system that supplied part ofour 99°'Tcrequirements was also loaded with (n,y)99Mo supplied by General Electric, we investigatedthe contamination found in this aomTc. The °°Moused in the generators and the liquid—liquidextraction system was prepared from the same batch of

enriched 9tMo (personal communication from General Electric Co.).

The elution patterns of the identified contaminantswere determined by taking 1 ml of each eluate andsetting it aside for 1 week before counting on theGe(Li) system. These evaluations were carried outon generators eluted either once or twice daily, thesecond elution being 3 hr after the first. Half-lives

Received Dec. 3, 1975; revision accepted April 18, 1976.For reprints contact: M. W. Billinghurst,Health Sciences

Centre, 700 William Ave., Winnipeg, Manitoba, Canada R3E0Z3.

840 JOURNAL OF NUCLEAR MEDICINE

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TABLE 1.CONTAMINANTS INGENERATORPRODUCTGeneratorcalibrafion

date1311 (@aCi) @°‘Ru(@&Ci)@“Np(j@Ci)February

28toMarch280.2 —0.4 0.04—0.070.02-0.2April

4 to May 20.02—0.040.002—0.010.03—0.1May9toSeptember

190.08—0.1 0.02 —0.040.02-0.2

INSTRUMENTATION AND PHYSICS

Analysis of samples taken from each elution offive generators, eluted once daily, showed that theelution pattern of each radionuclide was reproducible, with only the quantity being eluted varying fromgenerator to generator. These patterns are shown inFig. 1 (the vertical axis is in arbitrary units and doesnot indicate the relative proportions of the different

nuclides).Analysis of samples taken from each elution of

five generators, eluted twice daily (3 hr apart),showed that:

I . The amount of 1311in the first elution eachday correspondedwell with the amountof1311 in the eluate of the generators eluted

only once daily. The amount of 1311in eachsecond elution was approximately twothirds that in the first elution that day. (N.B.:The 9DmTcin the second elution was onlyone-third of the amount obtained in the firstelution since only 3 hr had been allowedfor regeneration.)

2. The amount of 103Ru increased steadily ineach elution, with the same rate of increasefrom elution to elution as was observed withthe generators eluted once daily. The finalelution contained twice as much 103Ru asthe final elution of the generator eluted oncedaily.

3. The quantity of 239Np in the first and second elution each day was approximately thesame. The quantity each day decreased inthe same manner as was observed with thegenerator eluted only once a day.

DISCUSSION

Iodine-131. The level of 1311in the 9OmTcproductof these generators was as high as 0.4 @Ciin thefinal elution. Since the elution profile suggests thatapproximately three times this amount could be expected in the first elution, and since these were either400- or 500-mCi generators calibrated for the Friday following delivery, the iodine figure represents amaximum of approximately 1.5 @Ciper curie of

were determined by repeated countings over a period

of approximately one half-life for each contaminantidentified, using a fixed geometry between thecounted vial and the detector.

The quantity of 1311present in the tested sampleswas estimated from the Ge(Li) spectrum of a sampie of Na'31! that was assayed in our calibratorand then serially diluted to approximately 0.1 @@Ci/ml. All other activity calculations were based on theestimated gamma response curve of the Ge(Li) detector. This estimated response curve was based onspectra of serial dilutions of assayed samples ofD9mTc and 1311 and calibrated samples of “°Coand134Cs together with their relative gamma-photonabundances(9).

RESULTS

Since the end of February 1975 we have beenconcerned by the appearance of peaks at roughly105, 225, 280, 365, and 495 keV (to the nearest5 keV) in the Ge(Li) spectra of quality-control samples taken from the 99Mo—9°@'Tcgenerators. Half-lifedeterminations gave values of 8. 1 ± 0. 1 days forthe peak at 365 keV and 39 ± 1 days for the peakat 495 keV, identifying them as due to 131! and

103Ru, respectively. The peaks at 105, 225, and 280keV all had a half-life of 2.35 ±0. 10 days. This,together with the fact that these three peaks alwaysappeared with the same relative magnitudes (10:I .1 : 1.1 ) , led us to postulate that all three gammaphotons could be attributed to the same emitter.If these relative magnitudes are corrected for therelative gamma-energy detector efficiencies (5.6:1. 19 : I ) , obtained from the Ge(Li) response curve,we obtain the relative gamma abundances of 1 :0.52:0.62. On this basis, we concluded that the contaminant was 239Np, which has a half-life of 2.35 days,a 22.8%-abundant 106-keV gamma photon, an11.8%-abundant 228-keV gamma photon, and a14.1 % -abundant 277-keV gamma photon. Theseabundances are in the required ratio of I :0.52:0.62.Neptunium-239 also has a 3.4%-abundant 209-keVgamma photon, which was observed on retrospectiveexamination of the spectra. The next most abundantgamma photon, 2. 1% at 334 keV, could not be distinguished from background.

Table 1 shows the contaminant levels detected inthe final elutions of all the generators tested duringthe period from the end of February until the end ofSeptember 1975. Iodine-i 3 1 was detected in the

u9mTc obtained by liquid—liquid extraction, but theamounts of 1311were too low to make quantitationpossible. Ruthenium-103 and neptunium-239 werenot detected in the product from the liquid—liquidextraction system.

Volume 17, Number 9 841

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BILLINGHURST AND HRECZUCH

the decayed alumina columns of the fission-productgenerators indicated that the ‘@‘Ilevels were at leastan order of magnitude below the specified maximum. Thus, if the fission-produced 99Mo used inthe generators were barely to meet specifications, theproduct from the generator might be unacceptable.

Ruthenium-103. In one case where the generatorwas eluted twice daily, the steady increase in 103Ruwith each elution resulted in a maximum level (inthe second elution on Friday) of 0.1 @Ciof 103Ru inabout 100 mCi of 99mTc Thus, the ‘°3Rucontamination level never approaches the maximum permissible level of 5 X 10@% of the 99mTc Ruthenium103 was also observed on the decayed columns ofthe generators, indicating that only a small percentage of the total amount was ever eluted off thealumina column.

The manufacturer's contamination analysis (11)lists a ‘@3Rulevel of 2 X i0@ % of the 99Mo oncalibration date. This is more than an order of magnitude below the limit for fission-product °9Mo(12,13) . However, as with 1311,the fission generators examined showed very little 103Ru in the eluate,and the Ge(Li) spectra of the alumina columnsshowed much lower levels of ‘°3Ruthan the maxi

mum permissible.

Neptunium-239. The presence of 239Npis not supported by the manufacturer's radioisotopic analysisof the parent 99Mo (1 1 ) . However, the neptuniumpeaks would be obscured by those of 9lmNb (104.5keV, half-life 62 days), ‘32Te(228 keV, half-life 78hr), and 1311 (364 and 284 keV, half-life 8 days),which are all present in the parent 99Mo. Iodine-13 1is, of course, present in the eluate as already discussed; however, its contribution to the peak at 280keV is small at the time of the intial Ge(Li) spectra.Continued observations of the 280-keV peak past

the first half-life showed an apparent increase inhalf-life due to an increasing proportion of 131!.

The typical elution profile for 239Np shows thatthe quantity of 239Np in each elution decreases at arate approximately equivalent to its rate of decay.Thus, up to 1.6 1@Ciof 239Np may be found in the

first elution. The maximum permissible level ofgamma-emitting impurities in O9mTc (other than99Mo, 103Ru, 131!,132I,and ‘34Cs)is 0.01 @Citotalper millicurie of 99mTc ( 10) . This is approximatelysix times what might be observed in normal dailyelutions but only twice what might be observed in asecond elution on any given day if it were performed

3 hr after the first elution.

The question is: “Wheredid the neptunium-239come from?― The manufacturer stated that the tar

get material used over this period was unfortunatelycontaminated with two parts per million of spent

Neptunium-239

Ruthenium-103

>.I->I-04LU>I-4-ILU

FIG.1. Typicalcontaminationlevelsof@ 1°@Ru,and“°Npintechnetium generators using (nçy)‘@Moon successive daily elutions.Note: Elution 6 is 3 days after elution 5. If ‘@Npvalue for elution6 is adjusted for extra 2 days of decay, it fits exponential curve.

0

ELLJTION NUMBER

99mTc at the time of the first elution. The maximum

permissible ‘@‘Iin “°@‘Tcat the time of injection is6 pCi per curie ( 10) ; thus, our material would exceed maximum permissible levels if administered 12hr after elution.

The presence of 131! in the parent 99Mo was confirmed from the manufacturer's radioisotopic analysis(11) . The 131Jconcentration reported in this analysis was 3 X I 0@% of the 99Mo on the calibrationdate. Atomic Energy of Canada (12) and UnionCarbide (13) , the major North American suppliersof fission-produced °°Mo,specify a maximum 1311contamination of 5 X 10@% on the calibrationdate. Thus, the maximum 1311that might be expectedin fission-produced 99Mo is an order of magnitudelarger than that reported for the (n,y) 99Mo used inour generators. Furthermore, since the alumina column used in most fission-product generators is

smaller than that used in a (n,y) °9Mogenerator,more contaminant breakthrough into the eluate

might be expected. We have examined the pertechnetate from fission 99Mo generators marketed bythree radiopharmaceutical companies (New EnglandNuclear, Charles E. Frosst, and Mallinckrodt/Nuclear) and have not found 1311 contamination atthe levels observed with the (n,y) 99Mo generators.However, an examination of the Ge(Li) spectra of

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INSTRUMENTATIONANDPHYSICS

ensure that the parent °9Modoes not contain enoughimpurities to yield a product that is unacceptable.On the other hand, “afterthe fact―testing is possiblefor any nuclear medicine laboratory and should becarried out as a routine procedure so that the qualityof the product is well established on a continuing

basis.

REFERENCES

1. ROBINSON GD: Impurities in @mTcsodium pertechnetate produced by methyl—ethyl—ketoneextraction. . I NuciMed 13:318—320,1972

2. AMWAR M, LAThROP K, ROSSKELLY D, et a!. : Pertechnetate production from @Moby liquid—liquidextraction.JNuclMed9: 298—299,1968

3. BILLINGHURST MW, GROOThEDDE M, PALSER R:Radiochemical purity of @mTcpertechnetate. I Nucl Med15: 266—269,1974

4. CROSBYEH : Radiochemical purity of short lived technetium-99m from commercial suppliers. Radiology 93 : 435—439, 1969

5. WooD DE, BOWEN BM : @‘Zrand “4Sbin @Mo—@mTc

generators. I Nucl Med 12: 307—309,19716. BARRALLRC: Reduction of radioactive impurities in

radiopharmaceuticals. I NucI Med 13: 570, 19727. PODOLAK EM : “Cs, @Rband @°Coin @Mo@@@mTcgen

erator eluate. I Nucl Med 13: 388—390,19728. SMITH EM: Properties, uses, radiochemical purity and

calibration of Tc@m.I Nucl Med 5: 871—882,19649. HEATHRK: Table of isotopes.In Handbook of Chem

istry and Physics, 4th ed. Cleveland, Ohio, CRC Press, 1973—

1974, pp B250—B54410. Information Letter No. 417 : Health Protection

Branch, Department of National Health and Welfare, Canada

11. General Electric Co. : Radiopurity analysis of General Electric lot No. 17

12. Atomic Energy of Canada: @Molybdenum specifications. February 12, 1974

13. Union Carbide : Fission product generator specifications

uranium before they received it (personal communication, 1975 ) . On this basis, we suggest that thefollowing nuclear reactions are responsible for the239Np:

238w + ‘n—@239U

(thermal-neutron cross section = 2.7 barns)

239U-4 239Np+ /3

(T,1, 23 mm).

Molybdenum-98 has a thermal-neutron cross sec

tion of 0. 14 barns. If we ignore the difference between the half-lives of 99Mo (66.6 hr) and 239Np

(56.5 hr) , we calculate that a contamination levelof approximately 40 @@Ciof 239Npper curie of 99Mowould be expected from the 2 ppm of uranium contamination in the °8Mo.This is about 25 times themaximum amount estimated for the first elution.

CONCLUSIONS

Iodine-i 31 , ruthenium-i03, and neptunium-239

were found in the eluates of u9Mo@@ftumTcgeneratorsloaded with °°Momanufactured by thermal-neutronirradiation of °8Mo.The level of contamination didnot exceed maximum permissible levels (10) at anytime, although on several occasions the contamination would have approached the maximum permissible levels less than 12 hr after elution.

Unfortunately, 131!and @9Npare not detected withadequate sensitivity in routine 99Mo breakthroughtests. Detecting 6 nCi of 131! per millicurie of 99mTcis difficult with equipment normally available in a nuclear medicine laboratory, and detecting 10 nCi of239Np per millicurie of u9nlTc is completely impossible. Therefore, the control of these impurities mustrest with the manufacturer. The manufacturer should

Volume 17, Number 9 843

ERRATUM

In the article “Thallium-201for Myocardial Imaging: Appearance of the Normal Heart―(J Nuci Med17: 583—589,1976), it was incorrectly stated that Dr. David J. Cook had been supported by a ClinicalResearch Fellowship from the Post-Graduate Committee in Medicine of the University of Sydney. Actually,it was Dr. Ian Bailey who had received this Fellowship. Also, the unit of measurement (cm) was omitted from

Table 2.

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1976;17:840-843.J Nucl Med.   M. W. Billinghurst and F. W. Hreczuch 

Mo99)-Produced γLoaded with (n, Tc Generators99nMo-99Np in the Eluate of 239Ru, and 103I, 131Contamination from

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