paffiation in this patient group might be associated withprolonged survival.

Samarium-153, a radionucide with medium-energy betaparticle emissions and a medium-energy gamma photon(103keV),isanappropriatecandidatefortherapeuticusein this setting. It can be attached to multidentate chelates toyield biolocalization similar to technetium bone agents foreffective delivery of beta particle energy directly to bonewith little soft-tissue dose. Pre-clinical studies in dogs thatreceived a high dose of ‘53Sm-EDTMPshowed spontaneous recovery of bone marrow function after a period ofpancytopenia (7). Because of this failure to effect marrowablation even at extremely high doses in the animal model,‘53Sm-EDTMPmay be useful in the treatment of patientswith bony metastatic disease in whom decreased bonemarrow function from disease involvement and prior treatment is common.

Samarium-153-EDTMP at low doses has been used elsewhere in the treatment of metastatic carcinoma to bone(8,9).WereportheretheresultsofaPhaseI trialof‘53SmEDTMP using escalating single doses in groups of fourpatients with hormone-refractory prostatic carcinoma metastatic to bone. Administered doses were higher than thosein previous trials and were designed to define limiting toxicity in this patient population. This report details the methods of preparation, administration, and biodistribution anddosimetry estimates of therapeutic doses of ‘53Sm-EDTMPfor pain palliation in prpstatic carcinoma. Specific details ofthe clinical parameters observed in these patients are meported elsewhere (10).

METhODS

Radlopharmaceutical PreparationSamarium-153(F11246.3 Kr, mean @—particle energies: 810

keV, 20%, 710 keV, 50%, 640 keY, 30% and 103keV gammaphoton, 28%)was produced at the University of MissouriResearch Reactor (MURR)from neutron irradiationof an enriched‘52Sm-oxidetarget (11). The target was dissolved in dilute HOand 300-800 mCi ‘53Smin HO was shipped for final preparationof the radiopharmaceutical.Samarium-153-Cl(specificactivity22—52mCi/ml) was added by injection into a lyophilized kit contaming217.2mgEDTMPusinga manualremotelabelingapparatus. The final product volume was adjusted by adding quantity

Frfty-twopatientswere treatedwfth singledoses of ‘@SmEDTMPin a PhaseI escalatingdoseprotocolfor palliationofbonepainfrom metastaticprostatecarcinomaSamailum-153çr11246.3hr),maximum@—paradeenergies810keV(20%),710keV(30%),640keV(50%),gammaphoton103keV(28%),wascomplexedto thetetraphosphonatechelate,EDTMP.Fivegroupsofpatentsweretreatedatdosesof 1.0,1.5,2.0,2.5,and3.0 mC@Ikgto evaluatetoxicityfrom trea@ent Patientswerescreenedpriorto treatmentandfollowedaftertreatmentwith

@Fc-MDPbonescans.BiOdiStilbUtlOndataon th@groupof@ntswere acquiredand showedrapki uptakeof 153@

EDTMPinto bonewith completeclearanceof nonskeletalrad@toxidtyby6-8 hr. @JsoinclUdedarecompletesetsofdosimetryestimationsonanadditionalsevenpatientswhoreceived0.5 mCi/kg1@Sm-EDTMPCa@ as part of a mumpledosetherapytrial.Estimatedradia@onabsorbeddosesto bonesurfacesaveraged25,000mred/mCi(6686Gy/MBQ),andunnaybladderdosesaveraged3600mradlmCi(964Gy/MBQ).

J NuciMed1993;34:1031-1036

atients with disseminated carcinoma often have painfulbone metastases. In these patients who have progressivedisease despite treatment, a systemic bone-avid radiopharmaceutical for treatment of widespread bony metastaseshas potential benefit. This has long been a goal in nuclearmedicine practice. Beginning with radiophosphorus, diverse radionuclides have been used but have not gainedwidespread acceptance because of myelosuppressive sideeffects (1—6).Patients with late stage hormone-refractoryprostatic cancer are an ideal group to derive benefit fromsystemic treatment of osteoblastic bone lesions with boneseeking radiopharmaceuticals. Once these patients havedeveloped hormone-refractory disease with painful bonymetastases, pain control becomes difficult and most patients die within 6—10mo of inanition associated with narcotic use and immobility. Because of this, effective pain

ReceivedNov.3, 1992;revisionacceptedFeb.25,1993.Forcorrespondenceorreprintscont@ J@etF.Eary,MD,AssociateProfes

sor, R@obgy and Patho$ogy,DM@onof NuclearMed@ne,UnivesltyofWashingtonMed@ Center,1959N.E.P@ñc,Seethe,WA98195.

Samarium-153-EDTMPin ProstateCarcinoma•Earyet al. 1031

Samarium-153-EDTMP Biodistribution andDosimetry Estimation

Janet F. Eat)', Carolyn Collins, Michael Stabin, Cheryl Vernon, Steve Petersdorf, Melissa Baker,Shelley Hartnett, Sandra Ferency, Stanley J. Addison, Frederick Appelbaum and Edwin E. Gordon

Depw1men@cofRadiolo@jtand Medith@ University of Wash@igtonMedical Center, Seattle, Washington,@Oak RidgeNational Laboratories, Oak Ridge, Tennessee; and Marion Me@rellDow, Indianapolis Indiana

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1@Sm-EDTMPdose groupNumber

ofpatients1@Sm (mCi)1@Sm(MBq)1.0mC@g2053—lOS1961-38951

.5mCI/kg4139—1765143-65122.OmCi/kg4147—2195439—81032.5

mCiilcg20149-2995513-110633.0mCVkg4224-2948288-10878

TABLE 1TreatmentGroups

Blodlstributlon Data CollectionAll patients received 25 mCi of @“Tc-MDP(Medi-Physics,

Emeiyville, CA) for bone scanning prior to treatment for localization of bony metastases. Whole-body scans with selected spotimages were obtained 3 hr after injection. A General Electric 500gamma camera with a dedicated Starcam computer was used forimage acquisition. The camera was centered over the 140 keVphotopeakwith a 13%window. A high-resolutioncollimatorwasused. Spot imageswere carefullyacquiredfor 10@counts/imagetodemonstrate lesional areas and normal areas for comparison. Twoto three regions of interest (ROIs) were drawn around representative areas of increased bony uptake for comparison of uptakewith identical normal bone sites. Uptakes were normalized tocounts/pixel for each site.

Twenty-four hour whole-body retention of the @‘@‘Fc-MDPdose was also calculated by comparing whole-body counts withthose of a @Tc-liquidstandard (12). These counts were obtainedwith a heavily shieldedthyroidprobeutilizinga 3-in. crystalaimedat the patient or standard15 feet away from the crystal surface.Background-subtracted counts were obtained immediately and at24 hr postinjection. These data were later compared with thecumulative urinary excretion of the ‘53Sm-EDTMPtreatment dose.

After infusion of the ‘53Sm-EDTMPtreatment dose, serialblood samples were withdrawn at 0.5, 1, 2, 4 and 24 hr afterinfusion for determination of percent injected dose/gram (%ID/g)in the serum. Aliquots of urine output in the catheter collectionbag were collected periodically for 24 hr. Total urine volumeswere recordedand each aliquotwas counted for determinationofcumulative percent injected dose excreted.

Patients were imagedjust prior to hospital discharge (24—43hr)after infusion of the ‘53Sm-treatmentdose. Whole-body scanswere acquiredwith the same spot views as the previous @“Tcbone scans. The camera was peaked at the 153Sm103 keV photopeak using the high-resolution collimator (Fig. 1). Spot imageswere acquiredfor 10@counts per image and the same ROIs wereapplied to lesional and nonlesional areas for determination oflesion-to-normal bone uptake. These data were compared with thelesion-to-normal bone ratios for the @“Tcbone scans acquiredprior to treatment.

Bone scans were obtained at 1, 3 and 5 mo while on study. Inrepeat bone scans, whole-body views and repeat spot views wereobtained for evaluation of disease progression. Lesion-to-normal

FiGURE1. Pt@―@@@of153Sm.

sufficient to make 6 ml of 0.05 M phosphate-buffered saline, withthe pH of the final product 7.0—8.5.Chelation yield of the kit wasdetermined by passage of 15—20@lof the final product over a0.6-ml SP Sephadex C-25 (Pharmacia LKB, Pleasant Hill, CA)column, where the chelate bound radionuclide eluted and free153Smwas bound to the column. A 1:10 dilution of the finalproduct was also tested for pyrogenicity using a limulus amebolysate assay (sensitivity 0.0125 EU/ml, Pyrotell. Assoc. of CapeCod, Woods Hole, MA).

PatientsAll patients had hormone-refractory prostate carcinoma. These

patients also had a Southwest Oncology Group performance status of at least 3, normal hematologic parameters and had notreceived maximum radiation to any local site. Any prior treatmentwith either radiotherapy or chemotherapy was completed 4 wkpriorto admission to this study. Since ‘53Sm-EDTMPhas identical sensitivity for metastatic lesions as visualized by @Tc-MDPbone scans, a positive @“Tc-MDPbone scan was required forentry into the treatment protocol.

This trial was carried out with the approvalofthe University ofWashington Human Subjects and Radiation Safety committees.Samarium-153 doses were administered to groups of four patientsat five escalating doses for determination of toxicity (20 patientstotal). To further define toxicity limits, an additional 16 patientswere treated at the 1.0 mCi/kg and 2.5 mCi/kg dose levels (32additional patients) (Table 1).

TreatmentPatients were treated as inpatients in standard hospital rooms.

After giving signed informed consent, with special attention to thepotential risks of toxicity from the treatment, patients had anintravenous line placed in each arm. One line was for infusion ofthe ‘53Sm-EDTMPtreatment dose, and the other was for serialblood sampling after dose infusion. Patients were hydrated withintravenous fluids for at least 6—8hr prior to infusion. Just beforeinfusion,patientshadindwellingthree-wayFoley cathetersplacedwith constant bladderirrigationfor 8 hr after infusion. The catheter remained in place for 24—48hr.

The ‘53Sm-EDTMPtherapy dose was placed in a 10-cc syringeand infused at a constant rate over 30mm by using an infusionpump(Harvard Appliances Inc., S. Natick, MA) that was housed in 1-in.thick lead shielding. Calcium gluconate for intravenous use wasavailable at the patient bedside in case the patient exhibited signs ofhypocalcemia from administration of the chelate. Vital signs weremonitored every 30 mm for 2 hr after the infusion, and then hourlyfor 4 hr. After infusion, the radiation safety officer surveyed thepatient room with a handheld dose rate meter and posted a map ofradiation dose rates atvarious positions in the patient room. Patientswere discharged from the hospital when dose rates at one meterfrom the patient indicated a body burden of 30 mCi or less; thisusually occurred 48 hr after treatment at the higher dose levels.

1032 TheJournalof NuclearMedicine•Vol.34•No.7 •July1993

52000Ct. (*4 HOSP OCR. SIS

26666

lO3keV21333

16000

10666

5333

5 1@_ 274 386 498keV

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bone uptake ratios and 24-hr whole-body uptakes of @“Tc-MDPEXPOSURE RATES 1-2 HOURS AFTER Sm-i 53-EDTMP

were also obtained for comparisonwith the pretreatmentevaluation assay.

DosimetryData for soft-tissue and skeletal dosimetry estimates in an

additional seven patients were also obtained. These patients received their therapy dose while lying under the large field of viewgamma camera. They received the ‘53Sm-EDTMPradiopharmaceutical formulation with Ca4@added so infusion was rapid (over1 min) with a handheldshielded syringe. Dynamic images of thechest and abdomenwere acquiredat a rate of 1 mm/framefor 60mm, followed by planar images at 1, 2, 24 and 48 hr postinfusionusing a general, all-purpose collimator. Images were accompaniedby serial blood samples, complete urine collection and bone biopsy at 24 hrpostinfusion. Additionally,patientswere counted forwhole-body retention of radioactivity daily.

Initially, gamma camera data were processed for generation oftime-activity curves with ROl placement over the lungs, liver,kidneys and several skeletal sites. Soft-tissue whole organ uptakewas determined using the opposing view planar quantitation technique. Since the soft-tissues were observed only anteriorly duringthe first hour, counts for the posterior whole organ views wereestimated using correction factors derived from other imagingexperience (13). After single organ time-activity curves were gencrated, it was noted that all sites had interference from associatedskeletal structures after 20 min. For dosimetry calculations, theinitial activity in an organ was assigned to be the activity measured in the 0—3-mmdynamic frames, and clearance was assumedto be the same as serum clearance. Normal and disease skeletalsite ROIS (humeral head, rib, sternum) were analyzed at everytimepoint for generation of time-activity curves.

Kinetic data were fit to a multicompartmentmodel using theSimulation Analysis and Modeling (SAAM) software (14). Themodel contained compartments representing serum, bone, kidneys and urinary bladder. Measured kidney activity data were notfit, but assigned, as discussed above. The kidney compartmentwas added to provide a realistic input to the urinary bladder.Residence times (15)were estimated fromresults of the compartment models and entered into the MIRDOSE2computerprogram(16). This program estimates radiation doses to the major organsbased on absorbed fractions for the adult male phantom in theCristy-Eckermanphantom series (17) using the standardMIRDtechnique (15), including the remainder of the body correction(18),thedynamicbladdermodelofCloutieretal.(19)andtheICRP 30dosimetry system for bone and marrow(20). It is importantto note that the phantomemployedhas a redmarrowmass of 1120g, not 1500g as in the MIRDPamphletNo. 5 adultmale phantom(21).Theurinarybladdervoidingintervalwas4.8hr.Tumoractivitykinetics were not included in the compartment model.

Skeletal doses were estimated from whole-body retentionwhere skeletal retentionwas assumed to be the inverse of urinaryclearance. Posterior iliac crest biopsies of lesional and normalbone were also obtained 24 hr postinfusion. Uptake was reportedas %ID/gby counting the biopsy and comparingit to an aliquotofthe injectate. Bone content was assumed to be 50%of the totalbiopsy weight (Appelbaum F, Bernstein I, Badger C, personalcommunication, 1989).

After counting, bone samples were embedded in methacrylate,sectioned and stained with hematoxylin and eosin. Sections werethen examinedfor presenceof tumorso thatuptakeof ‘5@Smin thespecimen could be ass@ed to lesionalor normalbone. Unstained

6

5

E4 . .@ •

@@ •:@

@ 5@o ióo 150 200 250 300 350mCiSm-153-EDTMPadministered

FIGURE2. Exposurerates1-2 hrafter1@Sm-EDTMPadministration.Rateswere measured1 meterfromthe patient.

sections from each biopsy were coated with NTB-2 (Kodak, Rochester, NY) autoradiographic emulsion and exposed at 4°Cin lighttight boxes for 1 wk. Following standard development, slides wereexamined for isotope deposition in association with bone.

RESULTS

RadlopharmaceuticalFifty-two ‘53Smdose aliquots were received from

MURR. All doses were complexed to the EDTMP kitwithout problems. Complexation yields were alwaysgreater than 99%, and all final products were pyrogen-freewith the limulus amebolysate assay. Seven doses of ‘53SmEDTMP Ca@@which were received as radiolabeled chelatehad similarquality control results.

Patient TreatmentSamarium-153-EDTMP doses were administered to 59

patients without problems. Radiation dose exposures atone meter from the patient after treatment are shown inFigure 2. In two patients, significant room contaminationoccurred when urinals were spilled. After these occurrences, all other patients remained catheterized followingtreatment until discharge.

BlodlstñbudonDathAs was previously observed (22,23), serum blood clear

ance half-time was rapid, with 4%—34%of the injected doseremaining in the serum 1 hr after infusion. The slow secondphase of serum clearance half-time ranged from 8.1 to 17.1hr (Table 2). Urinary excretion of ‘53Smwas essentiallycomplete by 6 hr after infusion. Urinary collection showed8.7%—64%of the injected doseexcreted in 10hr withoutsignificant variation between treatment groups (Table 2).The whole-body retention averages of the ‘53Sm-EDTMPtreatment dose group (estimated as [100% —the 24-hrcumulative urinary excretionj) were comparable to thosemeasured independently by whole-body counting, butwere considered to be the most highly accurate. Wholebody retention values were comparable with those of

@“@Tc-MDP,ranging from 47% to 76%. Pretreatment aver

1033Samarium-153-EDTMP in Prostate Caranoma •Eary at al.

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Sen.imClearanceU@na,y/Whde-body dearancePretreatmentLe@oo-to

24-hr Lesion-to normalboneTiaSlOW10-hr% remaining °°“@TC-MDPnormalbone1@Sm

153Sm

EDTMP

groupdearance

%ID at 1 hr phase(hr)cumulative%IDInunneinwhoie whole-body @rc-MDP

body at 10 hr uptake pro-treatmentEDTMPtherapydoseAvg.

±s.d. Avg. ±s.d.Avg. ±s.d.Avg. ±s.d. Avg. ±s.d. Avg. ±s.d.Avg.±s.d.1.0

mCi/kg6.6 3.1 4.7 2.237.4 13.762.6 13.7 49.9 16.8 4.8 3.94.93.01.5mCi/kg17.3 2.6 3.0 0.546.9 10.153.1 10.1 34.3 18.3 3.3 2.73.12.82.0mCi/kg6.0 1.4 7.3 4.523.8 15.076.2 15.0 53.0 16.1 2.9 1.92.71.92.5mCi/kg6.5 2.7 3.8 0.738.4 10.261 .6 10.2 53.0 12.0 6.0 5.74.63.63.0mO/kg10.0 3.6 3.9 0.637.4 22.262.6 22.2 57.3 22.6 6.5 5.06.74.1Avg.

istheaveragevalue for patientsand s.d. ise standardde@abonfortheaveragevaluesforeachgroup.

TABLE 2Samaiium-153-EDTMPB@diSthbUtiOnData

age 24-hr uptakes per group on @‘@Tcscans ranged from43.5% to 57.3% (Table 2). Scans ofthe ‘53Sm-EDTMPdoseobtained approximately 48 hr after treatment showed identical visualization of bony metastases (Fig. 3) comparedwith pretreatment @‘Tc-MDPbone scans. Average uptakeratios for @9'c-MDP and ‘53Sm-EDTMPby patient groupwere similar (Table 2). Follow-up 24-hr @Tc-MDPwholebody uptake values varied significantly from one patient tothe next and in the same patient over time (Fig. 4). Although there was a general trend of increasing skeletalretention of @“Tc-MDPin the scans at follow-up intervals,there was a great deal of variation in these measurements.Figure 5 shows changes in lesion-to-normal bone ratios on

@Tc-MDPbone scans after treatment. As with wholebody retention values, there is a great deal of variability.

W8 ANT WB POST WO ANT

5cr

Do@Organ residence times observed in patients studied for

dosimetry are shown in Table 3. Radiation dose estimates(Table 4) for soft tissues were similar to those estimated byLogan et al. (24) and Heggie (25), which were human dosesscaled from rat biodistribution data. Skeletal doses wereseveral fold higher, ranging from 20,000 to 32,000 mrad/mCi (5300-8800 Gy/MBq). Marrow doses ranged from4600to 7500mrad/mCi (1200-2000Gy/MBq) and urinarybladder doses ranged from 1300 to 4700 mrad/mCi (360—1300 Gy/MBq). Nonskeletal sites received negligibledoses. Four bone biopsies were obtained and showed 24-hr‘53Smcontent to range from 0.004 to 0.162 %ID/g bone.Autoradiographs of these specimens showed marked grainaccumulation in areas of osteoblastic activity and alongnormal trabecular bone deposition sites (Fig. 6).

FIGURE4. Technetium-99m-MDP24-hrwhole-bodyuptakesinthe patientsbydosegroupat baseline(pretreatment)andfollow-upat1and3moaftertreatment.Valuesdisplayedareaveragesforthefourpatientsineachgroup.

I'lb @U@I

Tc-99mMDP Sm-153EDTMPFiGURE3. Whole-bodyimagescomparevieualizationof bonymetastasesin the @rc-MDPbaselinescan (left)and @Sm-.EDTMPtherapydose(nght).

Tc-99m MDP 24 hour Whole BodyUptake after Treatment

0

4@0

..E U Imonth

@ U00

CS0.

6@

I .OmCilkg 1 .5mCi/kg 2.OmCilkg 2.5mCi/kg 3.OmCi/kg

Sm@153 EDTMP Treatment Dose Group

1034 TheJournalof NuclearMedicine•Vol.34•No.7 •July1993

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SourceOrganMeanResidencetime(hr)

standarddevietlonKidneys

(n =6)0.029±0.026Liver(n =7)0.021±0.010Lungs(n =6)0.020±0.010Skeleton

(n =7)*41.6±12.6Urinarybladdercontents(n=7)t2.56±1.10•ActMty

inskeletonequallydMdedbetweencorticalandcancellousbonefordosimetrycalculations.tBladdervoidingInterval4.8hr.

Tc-99m MDP Bone Lesion/NormalUptake Ratios after Treatment8

.2

.@ 8S

SC U b•••IIn•

@ 4@

. Imonth

. 3month

0z 20

.;0@1

I OmCi/kg I .5mCi/kg 2.OmCi/kg 2.5mCi/kg@ 3.OmCiikg

Sm-i53 TreatmentDose Group

:@@ s.;@._,1@ •@@ .@ -@;@@;...

@ @4

. 0' • •@•

@ @,

@ â€â€˜A

â€@1'@.@ - @.@ -,@@

,‘ -@

@TFiGUREt Twenty-fourhourpost-treatmentbonebiopsyautoradiographfroma patientwho received1@Sm-EDTMP.Markedgrainaccumulationaroundsitesofbonedepositionalongbonytrabeculaeis present.

FiGURE5. Lesion-to-normalboneratiosbeforeandaftertreatmentValuesareaveragesforeachgroup.

DISCUSSION

In this study, we demonstratedby imagingthat the biodistributions of ‘53Sm-EDTMPand @‘@‘Tc-MDPare verysimilar in lesional and nonlesional bone. Samarium-153 isas sensitive as the @Tcagent for visually identifying bonylesions. Whole-body uptakes and lesion-to-normal boneratios indicate that ‘53Smlabels normal and lesional boneto a similar degree and implies that patient selection fortreatment and follow-up by bone scanning with @‘9'c-MDP are appropriateand relevant with respect to ‘53Smdistribution.

Radiation absorbed doses estimated in a subset of thesepatients were similar to those estimated previously. Bonesurface doses were substantially higher than those predicted by extrapolation of the rat data, as were the marrowdoses. The primary reason for this difference is that thepatients with prostate cancer allowed in the study werethose with advanced hormone refractory disease. Overall,they had high skeletal retention ofthe administered activitybecause their multiple metastatic sites had exuberant osteoblastic activity. Skeletal radiation dose estimates were basedon whole-body retention, which reflects the contribution inuptake from both blastic metastases and normal bone. Theactive marrow dose was also higher than that predicted bythe animal data. Soft-tissue doses were considerably lower.

Total absorbed marrowdoses estimated by this methodranged from 1277 to 2250 rad in the 3.0 mCi/kg patientgroup. Two of four patients in this group experienced mildhematotoxicity (10). In canine and primate models, an cxternal beam total body irradiation dose of 200 rad results insevere myelosuppression and doses above 400 rad result inlethal myelosuppression (26). With ‘31I-labeledantibody,the dose of radiation required to ablate marrow appears tobe slightly higher, but doses of 200—400rad delivered tored marrow result in severe myelosuppression (27). Thisdiscrepancy between biological response and estimatedmarrow absorbed dose from ‘53Sm-EDTMPin the patientspresented here can be resolved by understanding the assumptions made by the bone dosimetry model and considering bone marrow microscopic anatomy. The ICRP-30dosimetry model estimates dose to marrow from the sourcedistributed on bone surfaces and assumes that all bonesurfaces are in contact with marrow. The bone dose in ourstudies was estimated from the whole skeletal radioactivecontent. In reality, the active marrow cell populations areheterogeneously distributed with respect to bone surfacesand fatty infiltration. In these patients with extensive, cxuberant osteoblastic disease, marrow in these metastaticareas may have received these high doses. However, marrow in normalbone, and particularlyin areas of nontrabe

TABLE 3OrganResidencelimes Observedin PatientsStudiedfor RadiationDosimetry

Samaiium-153-EDTMP in Prostate Carcinoma •Eary at al. 1035

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Targetorgan

mrad/mCiPatient

no.(Gy/MBq)12

3 4567Kidney150

(41)63 (17) 21 (6) 48 (13)40 (11)16 (4) 120(34)Uver21(6)27 (7) 19 (5) 16 (4)20 (6)16 (4) 16(4)Lungs36

(10)26 (7) 36 (10) 38 (10)30 (8)22 (6) 30(8)Ovaries29(8)37 (10) 33 (9) 35 (9)27 (7)32 (8) 34(9)Red

marrow7500 (2000)6000 (1600) 5500 (1500) 5000 (1400)6900 (1900)4700 (1300)4600(1200)Bonesurfaces32000 (8800)26000 (7000) 24000 (6400) 22000 (5800)30000 (8100)20000 (5400) 20000(5300)Testes16

(4)23 (6) 20 (6) 22 (6)15 (4)21 (6) 22(6)Urinarybladderwall1400 (390)4700 (1300) 4000(1100) 4500(1200)1300 (360)4600 (1200) 4600(1200)Target

OrganEstimated

radiationdosemrad/mCiGy/MBqMean

Standard deviationMeanStandarddeviationKidneys65

±5218±14.1Liver19±45±1.1Lungs31±68±1.6Ovaries32±49±0.9Redmarrow5700±11001514±261Bone

surfaces25000±47006686±1354Testes

Urinarybladderwall20±3

3600 ±15005 964±0.8 ±407

Sm-153chelates:potentialtherapeuticbone agents.I Nuci Med 1987;28:495—504.

12.DanaJ,CastronovoFP,McKuslckKA, GriffinPP,StraussHW,ProutOR.Total bone uptake in management of carcinoma of the prostate. I Urn!1987;137:444—448.

13. Easy JF, Press OW, Badger CC, et al. Ima@ng and treatment of B.celllymphoma. INuciMed 1990;31:1257—1268.

14. Robertson J. Conipamnentaldl@ttibutionofra&otrnce@c.Boca Raton, FL:CRC Press; 1983:73-142.

15. Loevinger R, Budinger 1, Watson E. MIRD p@ner for absothed dosecakidatioM. New York: Society of Nuclear Medicine; 1988.

16. Watson E, Stabin M. Basic auternath@esoftware package for internal radiatlon dose calculations. In: Kathren RL, Higby DP, McKinney MA, eds.Con!puter applications in health physics. Richiand, WA: Health PhysicsSociety; 1984.

17. Cristy M, Eckerman K. Spec4fic absorbedfructioas ofene@y at vaiiousages from intemaiphoton sowres. Oak Ridge, TN: Oak Ridge NationalLaboratoiy 1987.

18. aostier R, Watson E, RohrerR, Smith E. Calculating the radiationdose toan organ. INuciMed 1973;14:53-55.

19. aoutier R, Smith S. Watson E, et al. Dose to the fetus from radionuclidesin the bladder. Health Phys 1973;25:147—161.

20. Protection ICoR. Limitcforintakes ofradionuclidesby woi*e@ volume 30.New York: Pergamon Press; 1979.

21. Snyder W, Ford M, Warner0. Estimates ofspecific absorbed fractions forphoton sources uniformly distributed in various organs of a heterogeneousphantom.MlRDpamphlet no.5.1978.

22. Singh A, Holmes RA, Faranghi M, et al. Human pharmacokinetics ofsamarium.153-EDTMP in metastatic cancer. I Nuci Med 1989;30:1814-1818.

23. Faranghi M, Holmes R, Vorhut W, Logan K, Singh A. Samarium-153-EDTMP: pharmacokinetics, toxicity andpain response using an escalatingdose schedule in treatment ofmetastatic bone cancer.JNuclMed 1992;33:1451—1458.

24. Logan K, Volkert W, Holmes R. Radiation dose calculatious in personsreceiving injection of Sm-153-EDTMP. INuciMed 1987;28:505-509.

25. HeggieJ. Radiation absorbeddosecalculations for samarium-153-EDTMPlocalized in bone. JNuclMed 1991;32:840-844.

26. Appelbaum F, Brown P, SandmaierB, et al. Mtibody.radionucide conju.gates as part of a myeloablative preparative regimen for marrow transpiantation.Blood 1989;73:2202-2208.

27. Appelbaum F, Badger C, Bernstein I, et al. Is there a better way to deliver

total body irradiation? Bone Manvw Transplant 1992;10(suppl 1):77-81.

cular bone away from the bone surfaces likely received farless radiation, which can account for the mild toxicityobserved in patients in this study. The findings in this studysuggest that much higher doses of 153Sm-EDTMP are tolerable than predicted by conventional dosimetric estimates. As the role of ‘53Smin the treatment of bony metastases is defined, this agent may have a great deal ofpotential benefit in cancer patient management.

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1036

TABLE 4Samaiium-153-EDTMPRadiationAbsorbed Doses

TheJournalofNuclearMedicine•Vol.34•No.7•July1993

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1993;34:1031-1036.J Nucl Med.   Ferency, Stanley J. Addison, Frederick Appelbaum and Edwin E. GordonJanet F. Eary, Carolyn Collins, Michael Stabin, Cheryl Vernon, Steve Petersdorf, Melissa Baker, Shelley Hartnett, Sandra  Samarium-153-EDTMP Biodistribution and Dosimetry Estimation

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