Hindawi Publishing CorporationScience and Technology of Nuclear InstallationsVolume !"#$, Article ID $%&!'$, % pageshttp://dx.doi.org/#".##((/!"#$/$%&!'$

Research ArticleInfluence of the Generator in-Growth Timeon the Final Radiochemical Purity and Stability of99mTc Radiopharmaceuticals

L. Uccelli,1 A. Boschi,1 M. Pasquali,1 A. Duatti,1 G. Di Domenico,2 G. Pupillo,2

J. Esposito,3 M. Giganti,1 A. Taibi,2 and M. Gambaccini2

! Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale, Sezione di Diagnostica per Immagini,Universita di Ferrara and INFN, Sezione di Ferrara, Via Luigi Borsari "#, ""!$! Ferrara, Italy

$Dipartimento di Fisica e Scienze della Terra, Universita di Ferrara and INFN, Sezione di Ferrara, Via Saragat !, ""!$$ Ferrara, Italy% INFN, Laboratori Nazionali di Legnaro (LNL), Via dell’Universita $, %&'$' Legnaro, Italy

Correspondence should be addressed to A. Boschi; alessandra.boschi@unife.it

Received $#May !"#$; Accepted #$ August !"#$

Academic Editor: Mushtaq Ahmad

Copyright © !"#$ L. Uccelli et al.)is is an open access article distributed under the Creative CommonsAttribution License, whichpermits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

At Legnaro laboratories of the Italian National Institute for Nuclear Physics (INFN), a feasibility study has started since !"##related to accelerated-based direct production of &&mTc by the 100Mo(p,!n) &&mTc reaction. Both theoretical investigations andsome recent preliminary irradiation tests on 100Mo-enriched samples have pointed out that both the &&gTc/ &&mTc ratio and the&&mTc speci*c activity will be basically di+erent in the *nal accelerator-produced Tc with respect to generator-produced one, whichmight a+ect the radiopharmaceutical procedures.)e aim of this work was to evaluate the possible impact of di+erent &&gTc/ &&mTcisomeric ratios on the preparation of di+erent Tc-labeled pharmaceutical kits. A set of measurements with &&mTc, eluted froma standard 99Mo/ &&mTc generator, was performed, and results on both radiochemical purity and stability studies (following thestandard quality control procedures) are reported for a set of widely used pharmaceuticals (i.e., &&mTc-Sestamibi, &&mTc-ECD,&&mTc-MAG$, &&mTc-DTPA, &&mTc-MDP, &&mTc-HMDP, &&mTc-nanocolloids, and &&mTc-DMSA). )ese pharmaceuticals havebeen all reconstituted with either the *rst [ &&mTcO4]! eluate obtained from a 99Mo/ &&mTc generator (coming from two di+erentcompanies) or eluates a,er !-, $., -', and %! hours from last elution. Results show that the radiochemical purity and stability ofthese radiopharmaceuticals were not a+ected up to the value of ##.'- for the &&gTc/ &&mTc ratio.

1. Introduction99mTc, with its peculiar physical-chemical properties, stillcontinues to be the most important radionuclide used indiagnostic nuclear medical procedures. In particular, thedevelopments of technetium chemistry have opened newperspectives in the *eld of diagnostic imaging [#]. Morethan '"% of the radiopharmaceuticals are currently labeledwith this radionuclide [#] by reconstitution with sodiumpertechnetate [!–-] [Na99mTcO4] commercial kits containingin lyophilized form the various reagents required for thepreparation of each radiopharmaceutical. Its routine applica-tions are ensured by the availability of portable 99Mo/99mTcgenerators in which 99Mo is bound as molybdate anion

to alumina columns. Current global interruptions of 99Mosupply that involved uranium *ssion of highly enriched 235Utargets, aging reactors, and the staggering costs of theirmaintenance, focused on the search for alternative method ofthe 99mTc production [(]. One of the possibilities is to replacethe reactors with particle accelerators, aiming at a regionalproduction and distribution. At Legnaro laboratories of theItalian National Institute for Nuclear Physics (INFN), afeasibility study related to accelerated-based direct produc-tion of 99mTc by the 100Mo(p,!n) 99mTc reaction [., %] hasstarted since !"##.)eoretical investigations and some recentpreliminary irradiation tests on 100Mo-enriched samplespoint out that both the 99gTc/99mTc ratio and 99mTc speci*c

! Science and Technology of Nuclear Installations

T/012 #: Radiopharmaceuticals used in the study.

Name RadiopharmaceuticalNeurolite (Brystol-Myer Squibb) &&mTc-ECD (&&mTc-Bicisato)Cardiolite (Brystol-Myer Squibb) &&mTc-SESTAMIBIStamicis (IBA) &&mTc-SESTAMIBITechnemibi (Mallinckrodt) &&mTc-SESTAMIBITechneScan (Mallinckrodt) &&mTc-MAG$Pentacis (IBA) &&mTc-DTPAMedronato II (GE Healthcare)Osteocis (IBA)

&&mTc-MDP&&mTc-HMDP

Nanocoll (GE Healthcare) &&mTc-nanocolloidsRenocis (IBA) &&mTc-DMSA

activity will be basically di+erent in the *nal accelerator-produced Tc with respect to generator-produced one, dueto the concomitant production of Tc contaminant nuclides,such as 99gTc, 98Tc, 97mTc, and 97gTc. In particular, theamount of the ground-state long-lived !! emitter 99gTc,useless for diagnostic procedures,might have a negative e+ectin the radiopharmaceutical procedures going to competewith99mTc for the formation of the corresponding chemicallyidentical radiopharmaceuticals. )e presence of an excessof 99gTc might be responsible for a value of radiochemicalpurity lower than the standard required for some radiophar-maceutical preparations. In fact, the 99gTc present in solutioncould consume reagents of reaction, and in particular thereducing agent (SnCl2). As a result, unreacted [99mTcO4]!may remain in the solution, or radioactive by-products notuseful for the speci*c diagnostic procedure may be formed.)e quality of 99mTc is then fundamental for the assuranceof radiopharmaceuticals quality ['–#"].)e aim of this workwas therefore to perform a set of measurements with 99mTc,eluted from a standard 99Mo/99mTc generator, in order to *rstcheck possible impact of di+erent 99gTc/99mTc isomeric ratioson the preparation of di+erent Tc-labeled pharmaceuticalkits. Results on both radiochemical purity and stability stud-ies (following the standard quality control procedures) arereported for a set of widely used pharmaceuticals (i.e., 99mTc-Sestamibi, 99mTc-ECD, 99mTc-MAG$, 99mTc-DTPA, 99mTc-MDP, 99mTc-HMDP, 99mTc-nanocolloids, and 99mTc-DMSA).)ese pharmaceuticals have been all reconstitutedwith eitherthe *rst [99mTcO4]! eluate obtained from the 99Mo/99mTcgenerator (coming from two di+erent companies) or eluatesa,er !-, $., -', and %! hours from last elution.

2. Materials and Methods

)e preparation of radiopharmaceuticals reported in Table #was carried out with sodium pertechnetate eluates comingfrom two di+erent 99Mo/99mTc generators: a “dry” DRYTECgenerator (GE Healthcare, Via Galeno $. !"#!., Milan), anda “wet” Elumatic III generator (IBA-CIS Bio International,Route Nationale $"., Saclay BP $!, &##&! GIF SUR YVETTE,Cedex France).

All generators, with 99Mo calibrated activity of #"GBq,were eluted with (mL of saline solution as indicated by eachmanufacturer. From each generator, we analyzed and com-pared the three *rst elutions, performed just a,er generatordelivery (time elapsed between manufacturing and *rst usecan be estimate in !-$ days), and $ elutions were carried outa,er $., -', and %! hours from the previous elution.

$.!. Quality Control of 99Mo/99"Tc Generator Eluates. Gener-ator eluates have been subjected to all the tests [##] required byEuropean Pharmacopoeia [#-], and Italian Pharmacopoeia,#!th edn., Norme di Buona Preparazione dei Radiofarmaciper Medicina Nucleare, All. A, p.to A.! “Generatore di99Mo/99mTc (molibdeno/tecnezio)”.

$.!.!. Generator Elution Yield. It was expressed as % of theratio between the eluate radioactivity measured immediatelya,er elution using a dose calibrator ("#) and the theoreticalradioactivity ("$) calculated on the basis of the date ofcalibration and multiplied by the factor #"" [$]. )e elutione3ciency should be within the range of &"%–##"%.

$.!.$. Eluate Visual Inspection. All eluates were visuallyinspected, pulling the vial from its shielded container. )eoperation was performed within an adequately shielded cellfor radiopharmaceuticals manipulation; the vial containingthe pertechnetate eluate was manipulated by operators usinga pair of pliers to guarantee an adequate distance from thehands of the operator.

$.!.%. Eluate pH. Generator eluate is itself a preparation forinjection; ideally it should have a pH as close as possible to thephysiological, between % and '. )e Pharmacopeia requiresthat eluates have pH values within the range of -–'. Sincethe molybdenum is adsorbed onto the alumina in an acidenvironment, the pH values of eluates are slightly acid (-.(–.). It was measured by means of pH usual indicator strip(range "–#-) and checked by electronic pH-meter.

$.!.". Aluminum Content. It was determined by a semiquan-titative procedure employing indicator strips (Tec-ControlBiodex Medical, New York, USA) together with standardaluminium solution [#!, #$]. A drop of standard solution witha concentration less than (#gmL!1 of aurintricarboxylic acidwas deposited on indicator paper; subsequently, by side adrop of eluate was deposited. If the coloration produced bythe latter is lower than the one produced by the standard solu-tion, it can be assumed that the concentration of aluminiumin the eluate is less than the maximum acceptable level of( #gmL!1 provided by O3cial Pharmacopoeia [#-].

$.!.&. Radionuclidic Purity. Radionuclidic purity is the per-centage of total radioactivity which may be attributed tothe daughter radionuclide. In the case of *ssion-producedgenerator, the largest potential source of contamination thatcould exceed theminimum value detectable can be due to theparent (99Mo) [#(]. Trace amount of other *ssion impurities[#., #%] may be usually present in negligible amounts.

Science and Technology of Nuclear Installations $

!2

!"1

!""1

99Mo

99m Tc

99Tc

99m Tc !2 = 0.1154 hours#1 T1/2 = 6.0067 hours

P = 0.876

Decay of 99m Tc: IT $ = 140keV + IC (10%)

99Mo !1 = !"1 + !""1 = 0.010506 hours#1 T1/2 = 65.976 hours

F45672 #: Simpli*ed decay scheme of 99Mo to 99gTc.)e early and quick evaluation of the eluate content

of 99Mo was provided by the following procedure, whichinvolved the use of a lead shield of appropriate thickness("..mm of lead) in order to attenuate 99mTc emission [#'].)e activity contained in the unshielded elution vial wasmeasured with a dose calibrator (PET-dose, Comecer, Castel-bolognese, Italy); formeasuring 99Mo activity, the elution vialwas then placed within the lead shield and its activity wasrecorded. )e thickness of the shield was enough to largelyattenuate the #-" keV photons [#&], and only partly thosegreater than %"" keV. )e measured activity, multiplied by asuitable correction factor which accounts for the attenuationof %-"–%'" keV photons due to the lead shielding, providesan estimation of the 99Mo activity. )is value should notexceed ".#% of the 99mTc activity according to the EuropeanPharmacopoeia.

For a more accurate determination of the radionuclidicpurity [#%, !"], the same eluate sample was examined again(reassayed) a,er %–#( days by means of high-resolutiongamma spectrometry using a solid-state, high-purity germa-nium detector [#.].

$.!.#. Radiochemical Purity. It was checked by paper chro-matography, Whatman no.# paper strips and saline as mobilephase. According to this procedure, 99mTcO4! migrates withthe solvent front ($% = 1), whereas reduced hydrolyzed 99mTcremains at the origin ($% = 0).)e radioactivity distributionwas measured by a scanning radiochromatography detectionsystem for thin layer chromatography (Cyclone instrumentequipped with a phosphor imaging screen and an OptiQuantimage analysis so,ware (Packard, Meridien, CT)). Eluateradiochemical purity should be greater than &(%.

$.!.(. 99&Tc to Active 99"Tc Ratio. 99Modecays to 99gTc (#!.-%)and 99mTc ('%..%), and the latter, with a physical %1/2 of.."".% h, decays to 99gTc (%1/2 = !##,#"" years). Due tothis particular branching decay of 99Mo, even fresh elutionsfrom a generator always contain both isotopes (99mTc and99gTc), indistinguishable from the chemical point of view.)e amount (#g) of total technetium present in the eluate isdirectly related to the amount of 99Mo atoms present on thecolumn (i.e., 99Mo activity) and the time that elapsed sincethe previous elution. )e total number of Tc atoms, namely,the sum of 99gTc and 99mTc, has been calculated as follows:&Tc(total) = &'99Mo '1 ( )!(1)* , (#)

where&'99Mo is the initial99Mo atoms number present on the

column, +1 is the decay constant of 99Mo ("."#"( hours!1),and , is the time that elapsed since the last elution. )enumber of 99mTc atoms has been calculate as follows:&99mTc = - +1+2 ( +1&'99Mo ')!(1) ( )!(2)* , (!)

where +2 is the decay constant of 99mTc (".##-& hours!1) and- is the decay probability (- = 0.876). A simpli*ed decayscheme of 99Mo to 99gTc is shown in Figure #. From the aboveequations the number of 99gTc atoms can be easily calculatedas follows: &99gTc = &Total Tc ( &99mTc ($)

and thus the 99gTc to active 99mTc ratio can be estimated.)e determination of the 99gTc content in a fresh eluate

requires an immediate measurement a,er the elution ofthe 99mTc activity and a later measurement of the totalactivity of 99gTc (in a few months almost all the 99Moand 99mTc atoms decay into 99gTc). )e evaluation of 99mTcactivity in the sample has been performed by using a dosecalibrator (PET-dose, Comecer, Castelbolognese, Italy), whilethe evaluation of 99gTc activity has been performed usingthe TRI-CARB !'#"TR liquid scintillation analyzer (PerkinElmer Inc., Monza, Italy). )e samples for 99gTc activitymeasurements were prepared taking an aliquot of ".'mLfrom an eluate decayed for ." days (total volume of theeluate: (mL) and adding (.-mL of liquid scintillator (UltimaGold LLT cocktail, Perkin Elmer Inc., Monza, Italy). )emeasurement of 99gTc activity was performed using the "–!&( keV energy window.

$.$. Radiopharmaceuticals Labeling. )e elutions were usedto label di+erent commercial kits (Table #). Kits reconsti-tution was performed according to the methods describedin the package included within the commercial kits. )eradiochemical purity (RCP) of radiopharmaceuticals wasevaluated immediately a,er preparation (, = 0) and at theend of the stability period indicated by the manufacturer.)e radiochemical purity and stability were measured usingmethods speci*ed by manufacturer, with the exception ofTechneScan (Mallinckrodt) for which the following chro-matographic system was used [!#]: mobile phase, (-/-(/#(physiological/methanol/glacial acetic acid) and stationaryphase, RP-#' (Merck). )in-layer chromatography plateswere analyzed with a Cyclone instrument equipped with a

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T/012 !: pH, &&Mo, #"$Ru, and #$#I amounts and radiochemical purities (mean ± standard deviation) of the evaluated generators’ elutions.

Type of generator Type of elution pH &&Mo % #"$Ru % #$#I % RCP %

Drytec-GE

#' eluate 6.0 ± 0.3 (2.1 ± 0.2) . 10!2 (1.9 ± 0.2) . 10!6 (1.4 ± 0.4) . 10!7 99.8 ± 0.3$. h 6.0 ± 0.4 (3.9 ± 0.5) . 10!2 — 99.7 ± 0.3-' h 6.1 ± 0.3 (3.7 ± 0.4) . 10!2 — 99.8 ± 0.2%! h 6.0 ± 0.2 (3.1 ± 0.2) . 10!2 — 99.7 ± 0.3

Elumatic III

#' eluate 6.2 ± 0.1 (2.7 ± 0.3) . 10!2 (1.7 ± 0.5) . 10!7 (2.2 ± 0.3) . 10!7 99.8 ± 0.1$. h 6.2 ± 0.3 (2.5 ± 0.5) . 10!2 — 99.8 ± 0.3-' h 6.2 ± 0.4 (2.5 ± 0.1) . 10!2 — 99.6 ± 0.2%! h 6.1 ± 0.2 (2.5 ± 0.3) . 10!2 — 99.4 ± 0.1

E.P. -.'–'." <".#% <( . #"!3 <( . #"!$ /&(."E.P.: European pharmacopoeia; $., -', and %! h indicate the time from the previous elution; the amount of &&Mo represents the % of total radioactivity in thegenerators’ eluates determined with “rapid method”; #"$Ru (".-&%MeV) and #$#I (".$.(MeV) are the most common gamma radionuclide detectable by gammaspectrometry, and in the table are reported the % of total radioactivity in the generators’ eluates.

T/012 $: RCP of radiopharmaceuticals at , = 0, prepared with generator DRYTEC GE Healthcare eluates at time superior to !- h from thelast elution.

Commercial name Radiopharmaceuticals RCP$. RCP-' RCP%! RCP requirementsNeurolite &&mTc-ECD 98.57 ± 0.45 99.41 ± 1.51 98.73 ± 1.85 /&"%Cardiolite &&mTc-Sestamibi 97.91 ± 0.38 98.35 ± 1.02 99.40 ± 1.23 / &-%Stamicis &&mTc-Sestamibi 97.88 ± 0.28 97.90 ± 0.15 98.16 ± 0.11 /&-%Technemibi &&mTc-Sestamibi 98.18 ± 0.23 97.77 ± 0.33 98.53 ± 0.27 /&-%TechneScan &&mTc-MAG$ 98.89 ± 0.64 99.10 ± 0.44 99.31 ± 0.14 /&(%Pentacis &&mTc-DTPA 98.84 ± 1.01 98.91 ± 0.24 99.12 ± 0.33 /&(%Medronato II &&mTc-MDP 99.01 ± 0.24 98.44 ± 0.16 99.63 ± 0.64 /&(%Osteocis &&mTc-HMDP 99.22 ± 0.14 98.01 ± 0.52 99.13 ± 0.11 /&(%Nanocoll (PRC = -"min) &&mTc-nanocolloids 99.34 ± 0.09 99.38 ± 0.16 98.94 ± 0.41 /&(%Renocis &&mTc-DMSA 99.55 ± 0.08 99.22 ± 0.77 99.11 ± 0.03 /&(%RCP$.,-',%! indicate the radiochemical purity carried out with eluates obtained $., -' and %! hours a,er the previous elution.

phosphor imaging screen and an OptiQuant image analysisso,ware (Packard, Meridien, CT).

$.%. Imaging Studies. )ree 99mTc eluates produced by 99Mo/99mTc generator with di+erent 99gTc/99mTc ratio $ were usedfor imaging studies; the $ values were -.#., &.(#, and #(.!,respectively. Each tomographic acquisition has been per-formed by *lling a NEMA phantomNU --!""'with %-MBqof 99mTc-pertechnetate solution, and the data have beenacquired with the YAP-(S)PET small animal scanner proto-type [!!] and reconstructed by using an EM-ML algorithm.

3. Results and Discussion

)e results of the quality control (Table !) performed onall eluates obtained from two di+erent generator (DRY-TEC GE Healthcare and Elumatic III IBA) are consistentwith the European Pharmacopoeia requirements [#!]. Forsimplicity, data of visual inspection, yield of elution, andthe aluminum content in eluates are not reported, becausethey fell within European Pharmacopoeia requirements.

)e radiochemical purity (RCP) values of all radiopharma-ceuticals labeled with each eluate are reported in Tables$ and -. Results refer to the RCP evaluated immediatelya,er the preparation (, = 0). For simplicity, data atthe end of the stability period speci*ed by the manufac-turer are not reported, because they fell within the spec-i*cations required by the manufacturer. Tables ( and .report the RCP data obtained from reconstitution of the kitswith the *rst eluate. )e values refer to the checks carriedout immediately a,er the preparation (, = 0) and at theend of the stability period speci*ed by the manufacturer inthe package insert of each radiopharmaceutical. )e valuesof radiochemical purity are always superior to the standardsrequired by the manufacturer.)e results show that the totalamount of technetium (99gTc + 99mTc) present in the *rst elu-ate and in the eluates obtained at longer intervals, from !- hup to %! h, did not a+ect the radiochemical purity of the *nalproducts. Table % shows an estimation of the total amountof technetium present in an eluate obtained from a 99mTcgenerator with 99Mo calibrated activity of #"GBq. )e ratios$ of three 99mTc eluates at !- hours and two 99mTc *rst eluatesat -' hours have been measured, and the results have been$24 h = 3.23 ± 0.15 and$48 h = 6.68± 0.31, respectively.While

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T/012 -: RCP of radiopharmaceuticals at , = 0, prepared with generator Elumatic III (IBA) eluates at time superior to !- h from the lastelution.

Commercial name Radiopharmaceutical RCP$. RCP-' RCP%! RCP requirementsNeurolite &&mTc-ECD 98.77 ± 0.89 99.21 ± 0.71 98.68 ± 0.95 /&"%Cardiolite &&mTc-Sestamibi 97.88 ± 0.78 98.83 ± 0.92 99.13 ± 0.63 /&-%Stamicis &&mTc-Sestamibi 98.78 ± 0.23 98.90 ± 0.20 98.00 ± 0.19 /&-%Technemibi &&mTc-Sestamibi 98.45 ± 0.09 98.17 ± 0.23 98.11 ± 0.06 /&-%TechneScan &&mTc-MAG$ 99.79 ± 0.64 98.10 ± 0.44 99.44 ± 0.14 /&(%Pentacis &&mTc-DTPA 99.14 ± 0.12 98.88 ± 0.15 98.12 ± 1.03 /&(%Medronato II &&mTc-MDP 99.11 ± 0.33 99.44 ± 0.15 99.11 ± 0.43 /&(%Osteocis &&mTc-HMDP 99.01 ± 0.24 98.44 ± 0.16 99.63 ± 0.64 /&(%Nanocoll (PRC = -"min) &&mTc-nanocolloids 98.99 ± 0.03 99.18 ± 0.49 98.11 ± 0.11 /&(%Renocis &&mTc-DMSA 99.35 ± 0.22 98.67 ± 0.17 99.03 ± 0.29 /&(%RCP$.,-',%! indicate the radiochemical purity carried out with eluates obtained $., -' and %! hours a,er the previous elution.

T/012 (: RCP of radiopharmaceuticals at , = 0 and at the expired time speci*ed by the manufacturer, prepared with the *rst eluate obtainedfrom DRYTEC GE Healthcare generator.

Commercial name Radiopharmaceutical RCP (, = 0) RCPex RCP requirementsNeurolite &&mTc-ECD 99.17 ± 0.25 99.13 ± 0.21 /&"%Cardiolite &&mTc-Sestamibi 97.67 ± 1.24 97.71 ± 1.13 /&-%Stamicis &&mTc-Sestamibi 98.65 ± 0.40 98.57 ± 0.57 /&-%Technemibi &&mTc-Sestamibi 98.15 ± 0.11 98.01 ± 0.04 /&-%TechneScan &&mTc-MAG$ 98.79 ± 0.02 98.11 ± 0.15 /&(%Pentacis &&mTc-DTPA 99.03 ± 0.24 99.88 ± 0.11 /&(%Medronato II &&mTc-MDP 98.10 ± 0.13 98.02 ± 0.15 /&(%Osteocis &&mTc-HMDP 99.23 ± 0.18 98.15 ± 0.16 /&(%Nanocoll (PRC = -"min) &&mTc-nanocolloids 98.22 ± 0.13 98.33 ± 0.39 /&(%Renocis &&mTc-DMSA 99.28 ± 0.07 98.55 ± 0.21 /&(%RCPex indicates the radiochemical purity at the end of the expired time.

T/012 .: RCP of radiopharmaceuticals at , = 0 and at the expired time speci*ed by the manufacturer, prepared with the *rst eluate obtainedfrom Elumatic III (IBA) generator.

Commercial name Radiopharmaceuticals RCP (, = 0) (0 = 3) RCPex (0 = 3) RCP requirementsNeurolite &&mTc-ECD 98.38 ± 0.54 98.74 ± 0.25 /&"%Cardiolite &&mTc-Sestamibi 97.68 ± 0.56 97.77 ± 0.88 /&-%Stamicis &&mTc-Sestamibi 98.42 ± 1.02 99.03 ± 0.48 /&-%Technemibi &&mTc-Sestamibi 97.99 ± 0.11 98.15 ± 0.14 /&-%TechneScan &&mTc-MAG$ 98.11 ± 0.62 98.43 ± 0.29 /&(%Pentacis &&mTc-DTPA 99.16 ± 0.32 99.19 ± 0.11 /&(%Medronato II &&mTc-MDP 99.13 ± 0.04 98.77 ± 0.08 /&(%Osteocis &&mTc-HMDP 99.17 ± 0.12 98.76 ± 0.29 /&(%Nanocoll (PRC = -"min) &&mTc-nanocolloids 98.79 ± 0.16 98.92 ± 0.59 /&(%Renocis &&mTc-DMSA 99.11 ± 0.35 99.01 ± 0.32 /&(%RCPex indicates the radiochemical purity at the end of the expired time.

T/012 %: Evaluation of total technetium amount in &&mTc eluates coming from a generator with &&Mo calibrated activity of #"GBq, at di+erenttimes by previous elution.

Time by theprevious elution

Amount of totalTc calculated

&&gTc/&&mTc ratiocalculated

Amount of totalTc found

&&gTc/&&mTc ratiofound

%! h ".$" #g ##.'--' h ".!!#g ..(" 0.22 ± 0.01 6.68 ± 0.31$. h ".#'#g -.$-!- h ".#$#g !.(- 0.12 ± 0.01 3.23 ± 0.15

. Science and Technology of Nuclear Installations

(a)

(b)

(c)

F45672 !: Reconstructed SPECT trans-axial slices of NEMA NU --!""' *lled with 99mTc-pertechnetate solution. Top images (a) have$ = 4.16, middle images (b) have $ = 9.51, and bottom images (c)have $ = 15.2.the experimental value of *rst eluates at -' hours is in goodagreement with thetheoretical value of ..(, the experimentalvalue of eluates at !- hours shows a large di+erence withrespect to the theoretical value of !.((.)is discrepancy couldbe explained by taking into account the elution e3ciency1 = 0.91 of 99Mo generators used in our work. Indeed, therecalculated ratio$ at !- hours is included in the range (!.%'–$.$') and depends on temporal sequence of previous elutions.)e reconstructed SPECT images of NEMA phantom, for thedi+erent 99gTc/99mTc ratios$ used, are shown in Figure !.)eaverage reconstructed activity along the phantom axis, for thethree values of $, is shown in Figure $.)e visual inspectionon the images doesn’t show signi*cant di+erence in imagequality and radioactivity distribution. Currently, CERETECis the only commercial product for which the use of a fresheluate, obtained from a generator eluted for not more than!- hours, is required. )is exception is linked to the lowamount of tin chloride dehydrate in its formulation (%..#g),which makes its radiochemical purity strongly in8uenced bythe amount of 99gTc present in the eluate. All formulationsstudied possess signi*cantly higher amount of tin. A furtherlimitation to the use of eluates characterized by greateramount of 99gTc (elution intervals > !- h) could be due toradioprotection reasons related to the physical characteristicsof 99gTc (,1/2 = 2 . 105 y, !max = !&! keV). However

0.10

0.08

0.06

0.04

0.02

0.0010 20 30 40

Slice number

R = 4.16R = 9.51R = 15.20

Slice

activ

ity m

ean

valu

e (a.u

.)

F45672 $:)e average activity for reconstructed -" slices of NEMANU --!""' phantom *lledwith 99mTc-pertechnetate solution having$ = 4.16, $ = 9.51, and $ = 15.2.the amount of radioactivity associated with the mass valueis very low (e.g., ##g of 99gTc corresponds to .$"Bq).

4. Conclusion

In order to *rst check the possible impact of di+erent99gTc/99mTc isomeric ratios on the preparation of dif-ferent Tc-labeled pharmaceutical kits, the radiochemicalpurity and stability of 99mTc-Sestamibi, 99mTc-ECD, 99mTc-MAG$, 99mTc-DTPA, 99mTc-MDP, 99mTc-HMDP, 99mTc-nanocolloids, and 99mTc-DMSA were studied by using 99mTceluates coming from 99Mo/99mTc generator eluted at di+erenttimes from the previous elution.)e results prove that radio-chemical purity and stability of these radiopharmaceuticalsare not a+ected up to 99gTc/99mTc ratio of ##.'-.

A future goal will be to repeat the experiments with99mTc eluates coming from generators with 99Mo calibratedactivity higher than #"GBq, in order to check the possibleimpact of 99gTc in higher 99mTc activities solutions at di+erent99gTc/99mTc ratio.

Another future goal will be to study the impact ofaccelerated-based 99gTc and other Tc-isotopes on the imagequality and determine the allowed limit for 99gTc and otherTc-isotopes in the *nal accelerator-produced Tc.

Conflict of Interests

)e authors declare that they have no con8ict of interests.

Acknowledgments

)e authors would like to thank to Dr. L. M. Feggi (Unit ofNuclear Medicine, Sant’ Anna Hospital, Ferrara) for equip-ment and IBA-CIS Bio International, GIF SUR YVETTE,Cedex France for generators.

Science and Technology of Nuclear Installations %

References

[#] S. Banerjee, M. R. Ambikalmajan Pillai, and N. Ramamoorthy,“Evolution of Tc-&&m in diagnostic radiopharmaceuticals,”Seminars in Nuclear Medicine, vol. $#, no. -, pp. !."–!%%, !""#.

[!] O. P. D. Noronha, A. B. Sewatkar, and R. D. Ganatra, “Fissionproduced 99Mo- &&mTc generator system for medical use,” Jour-nal of Nuclear Biology and Medicine, vol. !", no. #, pp. $!–$.,#&%..

[$] N. Vinberg and K. Kristensen, “Fission Mo-&&/Tc-&&m gen-erators—a study of their performance and quality,” EuropeanJournal of Nuclear Medicine, vol. (, no. (, pp. -$(–-$', #&'".

[-] J. Vucina, “Technetium-&&m production for use in nuclearmedicine,” Medicinski Pregled, vol. ($, no. ##-#!, pp. .$#–.$-,!""".

[(] N. Knight, “Return of the radionuclide shortage,” Journal ofNuclear Medicine, vol. (", no. %, pp. #$N–#-N, !""&.

[.] J. Esposito, “Feasibility study report on alternative &&Mo/ &&mTcproduction routes using particle accelerators at LNL, (!""#version),” INFN-LNL-!$(, !"##.

[%] Report on the #st Research Coordination Meeting of IAEACRP Activities (code F!!".!), “Accelerator-based Alternativesto Non-HEU Production of 99Mo/ &&mTc,” Vancouver, Canada,April !"#!.

['] J. L. Vucina, “Radionuclide purity of &&mTc eluate for use innuclear medicine,” Medicinski Pregled, vol. -&, no. #-!, pp. -#–--, #&&..

[&] D. M. Hill, R. K. Barnes, H. K. Y. Wong, and A. W. Zaw-adzki, “)e quanti*cation of technetium in generator-derivedpertechnetate using ICP-MS,” Applied Radiation and Isotopes,vol. ($, no. $, pp. -#(–-#&, !""".

[#"] J. Bonnyman, “E+ect of milking e3ciency on 99Tc content of&&mTc derived from &&mTc generators,” International Journal ofApplied Radiation and Isotopes, vol. $-, no. ., pp. &"#–&"., #&'$.

[##] M. Marengo, C. Aprile, C. Bagnara et al., “Quality controlof 99Mo/ &&mTc generators: results of a survey of the radio-pharmacy working group of the Italian Association of NuclearMedicine (AIMN),”Nuclear Medicine Communications, vol. !",no. ##, pp. #"%%–#"'-, #&&&.

[#!] M. M. Webber, M. D. Cragin, and W. K. Victery, “Aluminumcontent in eluents from commercial technetium generators,”Journal of Nuclear Medicine, vol. #!, no. #", p. %"", #&%#.

[#$] A. M. Zimmer and D. G. Pavel, “Rapid miniaturized chromato-graphic quality-control procedures for Tc-&&m radiopharma-ceuticals,” Journal of Nuclear Medicine, vol. #', no. #!, pp. #!$"–#!$$, #&%%.

[#-] European Pharmacopoeia, %th edition, Sodium pertechnetate( &&mTc) injection (*ssion) ("#!-).

[#(] A. Hammermaier, E. Reich, and W. Bogl, “Chemical, radio-chemical, and radionuclide purity of eluates from di+erentcommercial *ssion 99Mo/ &&mTc generators,” European Journalof Nuclear Medicine, vol. #!, no. #, pp. -#–-., #&'..

[#.] P. Nasman and T. Vayrynen, “Impurities of &&mTc-generators,”European Journal of Nuclear Medicine, vol. ', no. #, pp. !.–!&,#&'$.

[#%] T. Vayrynen, P. Nasman, and K. Kiviniitty, “Residual activity ofTc-generators,” European Journal of NuclearMedicine, vol. ., no.., pp. !.&–!%#, #&'#.

[#'] S. Hoory, D. Bandyopadhyay, J.-C. Vaugeois, and L. M. Levy,“Impurities in generator eluates and radiopharmaceuticals: acomputerized quality assurance approach,” Health Physics, vol.(", no. ., pp. '-$–'-', #&'..

[#&] “Radiopharmacy and quality control pharmacists subcommit-tees of the regional pharmaceutical o3cers commitee. Qualityassurance of radiopharmaceuticals,”Nuclear Medicine Commu-nication, vol. #(, pp. ''.–''&, #&&-.

[!"] E. M. Podolak Jr., “134Cs, 86Rb, and 60Co in 99Mo- &&mTc gen-erator eluate,” Journal of NuclearMedicine, vol. #$, no. ., pp. $''–$&", #&%!.

[!#] I. Zolle, Technetium-))m Pharmaceuticals: Preparation andQuality Control in NuclearMedicine, Springer, Berlin, Germany,!""%.

[!!] A. Del Guerra, A. Bartoli, N. Belcari et al., “Performance eval-uation of the fully engineered YAP-(S)PET scanner for smallanimal imaging,” IEEE Transactions on Nuclear Science, vol. ($,no. $, pp. #"%'–#"'$, !""..

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