1993;34:2222-2226.J Nucl Med.   Hans Herzog, Frank Rösch, Gerhard Stöcklin, Christoph Lueders, Syed M. Qaim and Ludwig E. Feinendegen  Radiation Dose Calculation of Analogous Yttrium-90 RadiotherapeuticsMeasurement of Pharmacokinetics of Yttrium-86 Radiopharmaceuticals with PET and

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metastases (1—6),@°Yoffers some advantages: (1) it isavailable in a convenient generator system for no-carrieraddedsynthesis;and(2)manycompounds,includingcomplexes, chelates and particles (3,7—10)and monoclonal antibodies (Mabs) (11—18)can be labeled with @°Y.Recently,improvedchemistry for the productionof this radioisotopewas suggested (19,20). In spite of these advantages, twoimportantproblems remainunsolved which pertainalso toother beta-emitting radiotherapeuticals:the human pharmacokinetics as well as the internal radiation doses of@°Y-labeledradiopharmaceuticals are not known on a

quantitative level.The generalattemptto solve this problemis to substitute

90Y by an yttrium radioisotope detectable noninvasivelyfrom outside the body. Although ssY was studied in ammals (21,22) and 87Y in humans (23,24), no data aboutuptake kinetics or radiation doses were reported. BecausePET is capable of measuringbiodistributionquantitatively,the positron-emitting @Yis expected to be the yttriumradioisotope of choice (25). Recently, nuclear data relevant to the production of @Yvia the nuclear reactions

@Sr(p,n)and natRb(3He,2fl)as well as cyclotron irradiation,radiochemical processing and quality control were published (2427).

PET imagingwith @Y-citratewas performedon a patientsuffering from several bone metastases. The aim of thisstudy was to demonstrate that the application of anlabeled radiopharmaceutical in conjunction with PET measurements leads to quantitative data on localization anduptake kinetics, thus allowing calculation of radiationdoses to individual metastases and normal tissue in radiotherapy with the @°Yanalog.

SUBJECT AND METHODS

PatientThe patientinvestigatedwas a 37-yr-oldfemalein whom a

malignant tumor ofthe right breast had been diagnosed 1.5 yr ago.Inspiteof surgical,radiationandchemotherapies,numerousbonemetastases were found 10 mo later and further radiation therapyof the painfulbone lesionswas carriedout severaltimes. Plainx-ray film, computed tomographyand bone scintigraphywith

Thisstudywas performedtodemonstratethequantitativeinvivoassessment of human pharmacokineticsof @°Y-radiotherapeutics using the positron-emittingsubstitute @°Yand PET. Thistechnique is illustrated in a patient with disseminated bone metastases frombreast cancer who was injectedwith100 MBqofsey-citrateas an analog ofthe commerciallyavailablerad@therapeutic soY@citrate.Whole-bodydistilbutionwas measured witha PETcamera4, 10,21, 28 and45 hrpostinjection.Uptakedatawere determinedfromreconstructedtransverse PET images byregions of interest placed in normal bone tissue, liverand metastases. Images of coronal and sagittal whole-bodyse@onswere obtalned by reformathngthe transverse PET images. Theratio of activityconcentration in metastases to that in normalbone ranged from I 5: 1 to 3.5: 1. Of the injected tracer, 13.4%was found in the skeleton and 0.43% inthe metastasis withthehighest 80Yconcentration. Radiation doses per 1 MBqof injected @°Y-ciWatewere calculatedfrom @°Y-citratedata and datafromMIRDpamphlets5 and 11.The doses were 1.01MGy/MBqfor red marrow,593 @Gy/MBqforthe liverand —3.5MGY/MBqforthe most conspicuous metastases. This study demonstratesthat the use of PET via @°Yallowsan indMdualinvivoquantificationofactivityuptakeandradiationdose ofbothnormaltissueand tumor in pain treatment with @°Y-IthaledradiOtherapeuticS.

J Nuci Med 1993;34:2222-2226

his paper presents an in vivo method to assess thepharmacokinetics of @°Y-radiotherapeuticaquantitativelyusing the positron emitter @Y(Tia 14.74 hr,@ 33%,EpF,m@ 1.4 MeV) and PET. It focuses on a generalmethodological approach to obtain biodistribution, biokinetic and dosimetric data for @°Y-labeledcompounds invivo which can also be applied to other therapeutic isotopes.

Ofvarious beta-emitting radioisotopes, such as 32P, @Sr,1311, ‘53Sm or 1@Re, used for treatment of painful bone

ReceivedFeb.23, 1993;revisionacceptedAug.5,1988.Forcorrespondenceaid reprintscon@ HansHerzog,PhD,InstituteofMad

icine,Reseerch CenterJUlich,D-52425JUlich,Germany.

2222 The Journalof NudearMedicine•Vol.34 •No. 12 •December1993

Measurement of Pharmacokinetics of Yttrium-86Radiopharmaceuticals with PET and RadiationDose Calculation of Analogous Yttrium-90

RadiotherapeuticsHans Herzog, Frank ROsch, Gerhard StOcklin, Christoph Lueders, Syed M. Qaim and Ludwig E. Feinendegen

IrL@titiUesofMedicine and Nuclear Chemist,y, Research CenterJulich, Jülich,Gennany

by Frank Roesch on July 8, 2014. For personal use only. jnm.snmjournals.org Downloaded from

@Tc-DPD(@Tc-3,3-diphnspono-1,2propanedicarbonate)recorded before the PET examinationrevealed metastases in thefacial part of the head, the lung, the pelvis, the right femur and atdifferent locations in the spine. A palliative treatment with @°Ycitrate was performeddirectlyafter the PET investigation.

Preparation and Application of @V-CItTatBYttrium-86was produced at the Jülichcompact cyclotron

CV28 via the (p,n)-reaction on 96.3% enriched @SrCO3targetmaterialin theprotonenergyrangeof 14.2-. 10.2MeV(26,27).Chemical processing led to no carrier-added and radiochemicallypure @Y(III).Yttrium-86-citratewas synthesizedby addingonedropofaqueous &@Y(III)solutionto 2 mlofsodium citratesolution(7.5 mg/mI, final pH 74). The pharmaceutical was sterile ifiteredand apyrogenity was ensured by standard methods. Radiochemical quality control was performed by paper chromatography onMN21usingpyridine-to-ethanol-to-watermixtures(4:2:1)as solvent. The content of the @Y-citratecomplex was found to be>98%.Twelvehoursafterisotopeproduction,100MBqof @Ycitrate were injected intravenously.As detected by gamma..rayspectrometry, the radionuclide contaminants of @Y,namelyS7my 87y and @Y amounted to 1.9%, 0.75% and 0.1%, respec

tively, at the time of application.

Measurement and Data AnalysisFour hours after the injection of the radiotracer, the first PET

measurement was performed with a whole-bodyPET cameraPC4096-15WB (Scanditronix-GE, Uppsala, Sweden). This camera'sfieldofview hasa diameterof 55cmanda thicknessof 10.5cm in which 15 adjacent planes are recorded simultaneously.Performance characteristics have been described earlier by RotaKopset al. (28).In order to correct the acquiredemissiondata forattenuation, a sequence of transmission scans was obtained beforethe firstemissionscan.Thissequenceconsistedof fourteen3-mm transmission scans between which the patient's bed wasmoved 10.5 cm in the cranial direction so that the patient wasviewed from the head down to the most caudallylocatedmetastasis, with a lengthof 147cm. Sequences of 4-mis emission scanswith identicalmovements of the patient's bed were acquiredat 4,10,21, 28 and45 hraftertracerinjection(p.i.).Thepatientwasvety carefully repositioned in order to match the position during

the transmissionscan.The reconstructionof the emission data corrected for attenua

tion resulted in 210 PET imagesof transverseorientationfor eachmeasurement.The tracer accumulationin fiveprominentmetastases and normal bone was quantified by the region of interest(ROl)technique.ROIsoverthemetastasesweremanuallydefinedby comparingtraceruptakewiththeirlocalizationsseeninradiological images and bone scintigrams. The activity concentration ata specific uptake site was evaluated in three adjacent slices,averagedandcorrectedfor radioactivedecay.BecausePET measures only the positronemissions, which are33%of allradioactiveevents of 86Y, the activity concentrations found by PET weremultipliedby 3.0.

Inorderto display PETwhole-bodyviews ofthe distributionofMY-citrate,a computerprogramwas written, by which the transversal PET images were rearranged as described in the following:Each sequenceof 14x 15PET imageswitha matrixsizeof 256x256 were assembled in a three-dimensionalmatrixcontaining210x 256 x 256elements.The dimensionsof eachvoxel were 6.5 mmintheaxial(z)directionand2 mminthex/y-direction.Inordertoreduce the amount of storage needed, evety 2 x 2 pixels in theimage plane were combined by averaging. The resulting three

dimensionalmatrixwith its 210 x 128 x 128elements was filteredwitha three-dimensionalfilterkernel.Afterreadingthisfileby asecond program,any coronal or sagittal section with an area of147cm X 51.2 cm could be obtained. Inorderto achieve the samescale in the z-direction as in the x-direction or the y-direction, datain thez-directionwereinterpolated.

The calculationof the radiationdoses to the red marrow, theliverand the fivemetastaseswere performedalongthe linessuggested by the MIRD Committee (29). The decay-corrected pharmacokineticdata, i.e., percentageof injected @Yactivityperorganor per cm@tissue, were consideredto also be valid for the@°Y-labeledtherapeutic.By extrapolatingthis data until five half

timesof roy (‘@@)multiplyingthem with the decay functionandintegrating until T5, the cumulated activitiesA were obtained. Toget the percentage of injected activity in normalbone and liver,the activity concentrationprimarilymeasuredby PET was multipliedbytheorgan'svolumeasgivenby theMIRDCommitteefora humanweighing70 kg (30). Takingintoaccountthe patient'sweight of 75 kg, a bone tissue density of 1.5 g/cm@and a liverdensity of 1 g/cm@,the resultingvolume of the total bone wasabout3600cm3andthatof the liverwas 1900cmi.

The radiationdose to the liver was

@@ _, Liver

The radiationdose to the red marrow(RM), considered tobe caused by activity equally stored in cortical and trabicular bone, was obtained by:

D@ = A@e(0.5S@.@ -@P@I+@ ., pjv@).

The S-factorswere taken from MIRD Pamphletno. 11 (29)for @°Y.

The radiationdose to a metastasis DMetawith volume Yand mass M = Vp was calculated by:

@ AMeta@DMeta M = p

with AMeta cumulated activity per injected 1 MBq per 1cm3 of metastatic tissue;@ = absorbed dose fractiontimes dose constant for @°Y= 2 g raW(@Cihr) = 0.54 gGy/(MBq Kr); and p = bone density = 1.5 g/cm@.

Therefore, the dose to a metastasis is dependent only onthe activity concentration as measuredby PET and not onits volume.

RESULTS

Figure 1 (left part) displays an anterior view of the patient's body from the head down to the knee. As all coronalsections are summarized here, this image is equivalent tothe conventional whole-body scan obtainedwith a gammacamera. However, the data here are corrected for attenuation. The locations of increasedtraceruptakeare in agreement with the hot spots found in the bone scintigramswith

@Tc-DPD(Fig. 2). As expected, a generalbone uptakeof86Ywasfound.Furthermore, @Ywasobservedalsoin theliver. The rightpart of Figure 1 represents a sagittal 8 cmthick section in the median plane of the patient's body.Here the metastases in the spine are clearly displayed.

@°Y?°Y-Radiopharmaceuticalsand PET •Herzoget al. 2223

by Frank Roesch on July 8, 2014. For personal use only. jnm.snmjournals.org Downloaded from

@i'cc15 I I

I@ Thorac@cSpine

Lumbar SpineRight Hip

12

@ Head

:@@ Knee3 @::::iii:iiiii6._..@_@__.____.@_a Normal Spine

@ Liver

0@@ I I I I0 10 20 30 40 50 60 70

Time (h)

0U

a-m

>@

>

U

FIGURE 3. Decay-corrected time-activitycurves of NY-citrate innormal bone (spine), liverand five metastases.

FiGURE 1. Whole-bodyimages ofthe distributionof@°Y-cftrateina 37-yr-oldfemaleat 10 hrpostinjection.Left.anteiiorviswwithallcoronal sections summed up. Right 8-cm thicksagittal section inthemedian plane of the patIent@sbody. The arrows indicate the fivemetastases which were evaluated.

tamed if @°Y-citrateinstead of @Y-citratehad been injected, these data yield a radiationdose to the nonalteredred marrowof 1008 @tGyper 1 MBq of injected @°Y-citrate.

In the anteriorwhole-body image (Fig. 1, left) the liver isclearly visible. In contrast to the bone uptake, the liveractivity decreased steadily from 10 hr to 45 hr postinjection. Withan activity concentrationof2.56 kBq/cm@and anestimated liver volume of 1900 cm@(see above), 4.5% ofthe injected dose was found in the liver at 4 hr postinjection. These dataresulted in a radiationdose of 593 @tGyper1 MBq of injected @°Y-citrate.

The uptake of @Yin the head metastases, the thoracicspine, and the right knee was nearly constant after 10 hrpostinjection. The metastases in the hip and the lumbarspine seem to accumulate @Yuntil 45 hr postinjection,however, the activity concentrations measured at 45 hrpostinjection are not statistically sound since they werevery low with a coefficient of variance of up to 100%.Furthermore, the error might have been enhanced by thedecay correction. Therefore, the calculation of radiationdose in bone and metastases assumed a constant activityconcentration after 10 hr postinjection. The activity concentrationfound in the metastases is higherthan in normalbone (spine) with a ratio between 1.5 and 3.5 :1 (Table 2).The maximum activity concentration was observed in themetastasis located in the lumbar spine with about 0.43% ofthe injected dose at 10 hr postinjection. For this calculation, the volume of the metastasis was determined to beabout 40 cm3by ROl measurements. The radiationdose tothe five evaluated metastases ranged from 2.1 to 3.5 mGyper 1 MBq of @°Y-citrate(Table 3).

DISCUSSION

In this study, 100 MBq of @Y-citratewere injected in apatient suffering from multiple bone metastases frombreast cancer. In spite of the low activity of the injectedtracerand a low abundanceof 33%positrondecays of @Y,

Table 1 summarizesthe quantitative,decay-corrected dataof @Yuptake in normalspine, liver and five differentmetastases. The coefficient ofvariance (i.e., s.d. related to themean)of the pixel activities in the single ROIs rangedfrom30% to 100%. The uptake kinetics of @Y-citrateare shownin Figure 3.

The activity concentration in the normalspine was practically constant with about 4 kBq/cm@from 10 hr postinjection until the last measurement at 45 hr postinjection.Using this activity concentration as representativefor normal bone, 13.4% of the injected yttrium was stored in theskeleton. As the same uptake data would have been ob

FiGURE 2. Bone sontigrams after inje@onof°@rc-OPDshowsbone metastases in the head, spine, peMs and knee.

2224 The Journalof Nudear Medidne •Vol. 34 •No. 12 •December 1993

z@I

*@ t

@ *@_@

I

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Timeof scan(hr)Normal spineLiverMetastasesHeadThoracic spineLumbarspineHipKnee4

102128452.94

3.723.963.964.112.46

2.732.402.192.018.91

9.158.499.099.787.26

10.3810.8010.3211.949.54

10.5311.6112.6014.647.50

10.509.96

11.7913.594.56

6.576.276.365.91

Timeofscan(hr)HeadThoraoc spineLumbarspineHipKnee43.02.53.22.51.5102.62.82.82.81.8212.12.72.92.51.6282.32.63.22.51.6452.42.93.63.31.4

RedMetastasesThoracicLumbarmarrowUverHeadspinespineHipKnee1

.010.592.943.343.473.372.12

TABLE IActMty Concentration (kBq/cc) of Yttrium-86 in Normal Bone, LJverand Five Different Metastases

be caused by @°Y-citrate.Because of the shorterhalf-lifeof86Y(14.7hr) comparedto thatof @°Y(64hr), theassumption of a constant storage of yttrium in the metastasis andthe skeleton is critical. This assumption is, however, supported by the results of Kutzner et al. (22). In our own datawe found a nearlyconstant activity concentration(corrected for decay)in the normal bone and in the metastasesinthe head, the thoracicspine and the rightknee. In the othermetastases, the results for the last measurement at 45 hrpostinjection differed from a plateau-like uptake. Theseresults, however, might be erroneous, because the ROldata revealed a very high noise level. Therefore, the increases in @Y-activitydo not disprove the assumption ofconstant storage ofyttrium in normal and tumor-containingbones.

In contrast to conventional approaches, where only atotal bone uptake of a radiotherapeuticis determined bythe difference of injected and urinarilyexcreted activity,the method reported here is able to yield individual doseestimates to the red marrowand to single metastases. Thecalculations of the radiationdose per 1 MBq of @°Y-citrateinjected, yielded 593 j.tGyfor the liver, 1008 @Gyfor thered marrowand about 3.5 mGy to the metastases with thehighest uptake. The radiationdose to these metastases wasmore than three times higher than the dose to the redmarrow. The calculation of the radiationdose is based onROI evaluationwhich yields average data for a metastasisin total. It is, however, expected that the radiationdose ishigher in those parts of a metastasis which show peaks oftracer accumulation.

The findingspresented in this paper for the first patienthave to be verified in a greater numberof cases and cornpleted with further data for blood clearance and urinaryexcretion. Furthermore,itwould be interestingto compare“@YfPET-evaluated―@°Y-citratewith other @°Ycorn

TABLE 3RadiationDose (mGy/MBq)of Yttrium-90to Red Marrow,

@ Liverand Five DifferentMetastases

the PET measurementsyielded quantitativedata on traceruptake in normal bone and metastases.

The short recording time of 4 min for each 10.5-cmsection of the patient's body and the low numberof coincidence events with a maximum of about 25,000 at 4 hrpostinjection and 3,300 at 45 hr postinjection for a singleplane resulted in a high noise level of the single reconstructed PET images. When these PET images were assembled into a largeset of three-dimensionallyfilteredvolume data, cross-sectional whole-body images with a verygood quality could be obtained. Similar images have recently been published by Dahlbom et al. (31). In theirstudy, ‘8F-fluorodeoxyglucoseandthe ‘8Fion were used astracers and the quality of the whole-body images was excellent. However, those authors injected 370 MBq of thetracer with 100% positron decays. Taking into accountthese differences, the quality of the whole-body images of86Yis surprisinglygood.

As expected, @‘Y-citratewas primarily taken up bybone. The accumulation in the various bone metastaseswas higher than in the normal bone with factors rangingbetween 1.5 and 3.5 :1 so that the metastases could clearlybe delineated. The results found for the liver in comparisonto those for the skeleton are understandablein terms ofdifferent uptake retention mechanisms of @Y-citratein thetwo organs concerned. Considering recent pharmacokinetic data on ‘53Sm-EDTMPin rats and humans (32—34)and first results of the biodistribution of @Y-EDTMPinrats (21), which both recorded a missing liver accumulation, one could avoid the @Y-activityuptake in the liver byreplacingcitrate with EDTMP.

Based on the quantitative data of uptake kinetics of@Y-citrate,radiation doses were calculated which would

TABLE 2Acth@tyConcentration of Ytttium-86 in Frye MetastasesNormalizedto ActivityConcentrationin NormalSpine

@V/@°V-Radiopharmaceuticalsand PET •Herzoget al. 2225

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pounds like @°Y-EDTMPand these with recently considered radiotherapeuticalslike ‘53Sm-EDTMP(5,32—34)or‘@Re-HEDP(6). For the latter compounds, tumor-to-boneratios have been found with animal research and/or con

15.Anderson-BergWT,SquireRA,StrandM.Specificradio-immunotherapy@ antibody in errthtroleukemic mice. Cancer

16. i@ihner'P@, Yang NC, Frenkel TL, et al. DOsimetIyand treatment planningfor @°Y-labeledantiferritinin hepatoma.Intl Radiat OncolBiolPhysventional

whole-body scintigraphy or SPEC!', which are. . - an'

similar to or better than the ratios found here for i -citrate.1988;14:10334042.

17. Kozak RW, Raubitschek A, Mirzadeh 5, et al. Nature of the bifunctionalchela@g agent used for radioimmunotherapy with yttrium-90 monoclonalantibodies:criticalfactors in determiningin vivo suivivaland organ toxic

@ CWICerR@S1989;49:2639-2644.18. Hird V. Stewart 35W, Snook D, et al. Intrapentoneally administered @°Y

@ledmonoclonal antibodies as a third line oftreatment ofovarian cancer.Aph@ 1-2trial:problemsencounteredandpossiblesolutions.BrICancerRather

thanto compareumci@iuiauiuuivia UU@dI@L@t f bo - tr tm t th fthisevan or ne pam e e , e purpo p pe

was to describe the methodology. Our example demonstrates that quantification of human pharmacokinetics andradiation doses of the therapeutically used beta-emitting. . - . . .isotope 90@r@spossible with PET measurements usmg itsbeta-emitting sister isotope @Y.1990;62(suppl

10):48-51.19. DietZML@HorwitzEP.Improvedchemistiyfortheproductionof yttri

um-90 for medical apphcaftons. IntIAj@l Radiat Isot 199243:1093-1101.20. Bray LA, Wheelwright EJ, Wester DW, et al. Production of@°Yat Hanford

[@stract]. I NuciMed 1991;32:1090.21. BeyerGJ,BergmannR,KampfG,MadingP.RoachF.Simultaneousstudy

of the biodistribution of radio-yttriumcomplexed with EDTMP and citrateligandsin tumour-bearingmice Nuci MedBid1992;19:201-203.1.

KaplanE, Fda IG,KotlowskiBR,et al. Therapyof carcinomaof theprostate metastaticto bonewith 32P-labeledcondensedphosphate.I Nuci22.

KutZner J, Mittas W, Grimm W. Verteiungsmuster bei ratten nach intravenöserinjektionvon @Y-vethindungen.NuciMed198i-,20:35-39.Med

1960;1:1—13.23. Buchali K, Haesner M, Lips H, Beyer GJ, ROach F, Pink V.Stronium-892.FirUsianN, MeilinP. SchmittCO.Resultsof strontium-89therapyinpa versus ‘°Y-citratefor palliationofskeletal metastases. Preliminaryresultsoftients

with carcinoma of the prostate and incurable pain from bone metas a controlled study [Abstracti. Eurl Nuci Med1991;18:529.tases:a preliminaiy report. Urni 1976;116:764-768.24. Kutzner J, Hahn K, Beyer GJ, Grimm W, Bockisch A, ROsIer HP.Szin.3.

KutznerJ, DShnertW, Schreyer1, GrimmW, Bred Mi, &cker M.tigraphische verwendung von @Ybei der @°Y-therapievon knochenmeYttrium-90zur Schmerztherapievon Knochenmetastasen.NuciMed 1981;tastasen. NuciMed1992;31:53-56.20:229-235.25.

Roach F, Beyer GJ. Langerlebigepositronen-emitter:einzelnukiideund4.EisenhutM, BerberichR, KimmigB, OberhausenE. Iodine-131-labeledgeneratorsysteme, herstellungamU-120-zyklotroninRossendorf radiochediphosphonates for palliative treatment ofbone metastases: II. PrellminaiymischestudiensowiemOglichkeitenfUrdie PET.ReportZjK-7451991;1-30.clinical

results with iodine-131 BDP 3. 1 Nuci Med 1986;27:i255-1261.26. RoschF, QaimSM, StocklinG. Nucleardata relevantto the productionof5.GoeckelerWF,EdwardsB,VolkertWA,HolmesRA,SimonJ,WilsonD.the positron emitting radioisotope ‘@YViathe @Sr(p,n)-andnatRb(3He,2n)-Skeletal

localization of samarium-153 chelates: potential therapeutic boneprocesses. Radiochim Acta1993;61:1-8.agents.I NuciMed 1987;28:495-504.27. RoachF, QaimSM, StocklinG. Productionof the positronemittingradio

6. KetringA. ‘53Sm-EHDPand @Re-HEDPasbonetherapeuticradiophar isotope @Yfor nuclearmedicalapplication.IntlAppiRadiat Isot1993;44:maceuticals.NuciMed Biol1987;14:223-232.677-681.7.

DunscombePB, RamseyNW. Radioactivitystudieson two synovectomy28. RotaKopsE, HerzogH, SchmidA, Holte5, Feinendegen11. Perfors@ens afterradiationsynovectomywithytthum-9osiicate.AnnRheummance charactedsticsof aneight-ringwhole-bodyPETscanner.IAssLctDLc

198539:87-89.Co,nput Tomogr1990;14:437-445.8.BowenBM,DarracottJ, GameitES,TomlinsonRH Yttrium-90Citrate29. Snyder WS, Ford MR. Warner 0G. Watson SB. “5,―absorbed dosepercolloid

for radioisotope synovectomy.A IHospPhann 197532:1027-i030.unit cumulatedactivityfor selectedradionuthdesand organs.MIRDpam9. Greiff R. Zur durchfuhrung der schmerztherapie von knochenmetastasenphiet no. 11. New York: Society of Nuclear Medicine,1975.mit

@°Y-zitrat.NuciMed 1989;1:93—96.30. SnyderWS, Ford MR. WarnerGO, Fisher HL, Jr. Estimatesofabsorbed10.ShapiroB,Andrcwsi,FiggL,etal.Therapeuticintraarterialadministrationfractions formonoenergeticphotonsourcesuniformlydistributedinvariousofyttrium-90glass

microspheresfor hepatictumours[Abstractl.EurlNuc!organs of a heterogeneousphantom. MIRDpamphletno. 5. 1 NucIMedMed1989;8:401.1969;10(suppl.3):5—52.11.

HantovitchDJ,VirziF, DohertyPW.DTPA-coupledantibodieslabeled31. DahlbomM,HoffmanEl, HohCK,et al.Whole-bodypositronemissionwithyttrium-90.I NuciMed 1985;26:503—509.tomography: part I. Methodsand performancecharacteristics.INuclMed12.

Vaughan ATM, Keeling A, Yankuba SOS. The production andbiological199233:1191-1199.distributionof ytthum-90-labeledantilxxlies.Int JAppi Radiat Isot 1985;32. TurnerJH, MartingdaleAA, Sorby P. et al. Samarium-153-EDTMPtherapy36:803-806.ofdisseminated

skeletal metastasis. EurlNuciMed1989;15:784-795.13.WashburnLC, Sun U Hwa, Crook JE, et al. Yttrium-90-labeledmonoclo 33. SinghA, HolmesRA,FarhangiM, et al. Humanpharmacokineticsofnal

antibodiesfor cancer therapy.Nuci Med Bid 1986;13:453.samarium-153-EDTMP in metastatic cancer. I Nuci Med1989;30:1814-14.OrderSE,KleinJL,LeichnerPL,FrinkeJ, Lob C,CarloDi. Yttrium1819antiferritin—a

new therapeutic radiolabeledantibody.mt i Radial Oncol34. EaiyJ, CollinsC, StabinM,et al. Samarium-153-EDTMPbiodistributionBidPhys 1986;12:277-281.and dOShnetiyestimation. INuciMed 1993;34:1031-1036.

_1@@_____@@ t-pl_

2226 TheJournalof NudearMedicine•Vol.34 •No. 12 •December1993

REFERENCES

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