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25. MakrigiorgosGM, AdelsteinSJ, KassisAl. Limitationsof conventional Med 1983;24:l164—1175. internal at the cellular level. JNuclMed i989;30:1856—1864. 30. FeinendegenLE.HighLET-emittersand their relativebiologicaleffective 26. FenechM, MorleyA. Measurementofmicronucleiin lymphocytes.Mzaat ness. In: SchubigerPA, Hasler PH, eds. Radionuclidesfor therapy. Pro Res l985;i47:29—36. ceedings ofthe 4th Bottstein colloquium; Villigen, Switzerland; June 13— 27. Aimassy Z, Krepinsky AB, Bianco A, Kotcies Gi. The present state and 14,1986:39—57. perspectives of micronucleus assay in protection. A review. Appl 31. Cole J, ArIeti CF, Green MHL Ctal. Comparative human cellular mdi Radiat Isot l987;38:241—249. osensitivity. II. The survival following gamma- of unstimulated 28. Cole A. Absorptionof 20-eV to 50,000-eVelectronbeams in air and (G0) T-iymphocytes, T-lymphocyte lines, lymphoibiastoid cell lines and . Radia: Res 1969;38:7—33. fibroblasts from normal donors@from -telangiectasia patients and 29. Kassis Al, Adeistein Si, Haydock C, Sastry KSR. Thallium-201: an exper from ataxia-telangiectasia heterozygotes. mt i Radiat Biol l988;54: imental and a theoretical radiobiological approach to dosimetry. I Nuci 929—943.

SELF-STUDY TEST and Questions are taken from the Nuclear Self-StudyProgramI, published by The Society of DIRECTIONS The followingitems consist of a question or incomplete statement followedby fivelettered answers or completions. Select the one lettered answer or completion that is best in each case. Answers may be found on page 1182.

Truestatements concerning radiation-induced thyroidcancer 17. The limitingtissueresponseoccursinthe bonemarrow. include: 18. Radiationnephritisoccursinabout5% ofpatients. I . Alltypesofthyroidcancerareincreasedinincidenceby 19. Cytogeneticchangesincirculatinglymphocytesaredirect . ly related to the blood dose. 2. Itis unlikelyto develop as a consequence ofadministra 20. Radiation-inducedvomitingoccurs inmore than 20% of tion of 1311in dosesusedin the diagnosisor therapyof patients. thyrotoxicosis. 3. Itcan be distinguishedfromthatoccurring spontaneously. Radiation-relatedeffectsfrom high-dose32@therapyof 4. Itismorelikelytoresultfromexposuretothethyroiddur ing adolescence than in early childhood. polycythemia vera include: 5. Itis more common followingexternalthan internalradia 21. thyroidcancer tion exposure. 22. leukemia 23. leukopenia True statements concerning probability of causation (PC) calculations for radiation-induced include: Truestatements regarding radiationtherapy withradiolabeled 6. Theypertaintoaparticularcancerdiagnosedata particu lar timefollowinga particularradiationexposure. monoclonal antibodies include: 7. The PC is equal to the relativeriskfor radiation-induced 24. Itis effectiveprimarytherapy forseveral types ofcancer. cancerdividedbythesumofthatriskandthespontaneous 25. The radiation dose distributionwithina typical tumor is risk. sufficientlyuniformtoensureatumoricidaldosethrough 8. They may be applied to patients exposed to diagnostic out the tumorvolume. and therapeuticradiation. 26. The doseto normaltissues does notlimittheeffectiveness 9. Theyconsiderage,sex,andcigarettesmokinghabitsas of radiolabeled monoclonal antibodies as a sole method wellas radiation exposure. of treatment. 10. Theyare basedon the linear—quadraticmodelforall 27. Alpha-emittingradionuclides are preferred. cancers. For radiation protection purposes it is generally assumed that Iodine-131therapy forcarcinoma ofthe thyroidhas been shown a dose to a portion ofthe bone marrowcan be averaged over to cause the entire marrow. Concerning this concept, I I . excessdeathsfromcancerofthebladder. 28. a dose of 800 rads to 40% of the marrow is equivalent 12. excessdeathsfromleukemia. to 320 rads to the whole marrow. 13. increasedincidenceofmalignantsalivaryglandtumors. 29. the dose calculatedinthisfashionisthe same asthe mean 14. reducedfertility. marrow dose. I 5. overtevidenceofgeneticdamage. 30. the assumptionisconsistentwitha dose-response model incorporatingquadraticterms. 31. the assumptionappliesif partialbody doses are high True statements concerning 1311therapy for thyroid enoughto killcells. Include: 32. the assumptionisthe basisofthe dose equivalentconcept. I 6. Radiationeffectsontheparathyroidglandsoccurinabout 10% of patients. (continued on page 1182)

1174 The Journal of Nuclear Medicine•Vol.33 •No. 6 •June 1992 REFERENCES 1989;l73:469—475. 6. HashimotoY, StassenJM,LcclefB,ct al.Thrombosisimagingwithan I- I. Hui KY, Haber E, Matsuda GR. Monoclonalantibodies to a synthetic 123-labeled F(ab'h fragment ofan antihuman fibrin monoclonal antibody fibrin-like peptide bind to human fibrin, but no fibrinogen. Science in a rabbit model. 1989;ill:223—226. i983,222:l129—1132. 7. Rosebrougji SF, McAfee JO, Grossman ZD, et al. Thrombosis imagins@a 2. Rosebrough SF, Grossman ZD, McAfee JG, et al. Aged venous thrombi; comparison of radiolabeled GC4 and T2G1S fibiin-specific monoclonal radioimmunoimagingwith fibnn-specific monoclonal antibody. Radiology antibodies. JNuclMed 1990;31:1048-l054. l987;l62:575—577. 8. Rubin RH, FischmanAS,NeedlemanM, et al. Radiolabeled,nonspecific, 3. Knight LC, Maurer AH, Ammar IA, et al. Evaluation of indium-ill polyclonai human immunogiobulin in the detection offocal inflammation labeledanti-fibrinantibodyfor imagingvascularthrombi.J NuclMed by scintigraphy with gallium-87 citrate and -99m-iabeled albu i98829:494-502. mm. JNuclMed 1989;30:385—389. 4. Rosebrough SF, Grossman ZD, McAfeeJG, et al. Thrombus ima@ngwith 9. KairemoK.JA,WiklundTA, LiewendahiK, MiettinenM, HeikkonenJJ, indium-ill and iodine-13i-iabeledfibrin-specificmonoclonal antibody Ct al. Imaging ofsoft-tissue sarcoma with indium-ill-labeled monocional anditsF(ab'handF(ab)fragments.JNuclMed 198829:l2l2—l222. antimyosin Fab fragments. INuc/Med i990,3i:23-3l. 5. Jung M, IGetterK, DudczakR, et al. Deep veinthmmbosis scintigraphic 10. FlschmanAJ. When magic ballets ricochet[Editorial].I NucI Med diagnosiswith In-ill-labeled monoclonal anti-fibrin antibodies. Radiology l990;3l:32—33.

(continued from page 1174) SELF.STUDY TEST Radiobiology and Radiation Protection Questionsaretakenfromthe NuclearMedicineSelf-StudyProgramI, published by The SoCietyof Nuclear Medicine

Yournuclear medicine clinic operates from 8AMto 5PMMon 34. The amountof O9mTcspilledis sufficientlygreatthatthe day through Friday and is closed on Saturdays and Sundays. person whocleans up the debris and decontaminatesthe On Friday afternoon at 1PMa technologist who was prepar areashouldwearleadgloves,a leadapron,andspecial ing 9@mTcmacroaggregated albumin dropped the (99mTc] disposable clothing. pertechnetate stock vial. The vial, which contained 20 GBq 35. Theexposurerate(mR/hour)inthedosecalibrator/dose (about 500 mCi) of (99mTcJpertechnetate, broke and its con preparationareawill be sufficientlygreatto requirethat workinthisareabediscontinuedfortheremainderofthe tents splashed on the floor,the wall, and the adjacent cabinets. day. The contaminated area was infrontofthe radioactive material 36. Thecontaminatedareashouldbecompletelydecontami storage and waste disposal area, which is about 4 m from the natedtobackgroundlevelsbeforeleavingfortheweekend dose preparation area and the dose calibrator. Which of the sothathousekeepingpersonnelwill not be exposedto following statements concerning this accident are true? excessive radiation levels. 33. The amountof99―Tcspilledistoolargetobe ignoredand to be allowed to decay to background levels.

SELF-STUDY Skeletal NuclearTESTMedicineAN$WIR$

ITIN$ 1—5iRdlatlon-lnducd ThyroIdCancer ITIMI S—lOiCalculatIngProbabllftyof Causation ANSWERS:1, F; 2, T;a F; 4, F; 5, T ANSWERS:6,@7,1@8,F;9,1@10,F Thyrcidcancer,in @spapillaryform,isthepredominantradia@on-inducedTheradioepidemiologictablesthat provideprobat@lftyofcausation(PC) entity, with a lesser increase in follicular cancer. The incidences of values were designed to estimate the likelihood that a person who has medullaryand anaplasticcancersare notincreasedby radiationex orhashada “radiation-related―cancerandwhoreceiveda specific posurs The etiologyofindividualcases ofthyroidcancer cannot be at doseof radiationpriortoitsonsetdevelopedthediseaseasa resultof tnbutedtoradiationbyanypathologicalcriteriacurrentlyknown.Expo theirradialon.Proba@yofcausalontablaspertalntoaparticularcancer sureto1311hasnotbeenshowntocauseanincreasedincidenceofthyroid in a particular individual. cancerinmedicallytreatedhumansubjects,whereasx-raytherapyhas Therelativeriskperunitofradiationdosecanbeusedtodetermine been shownto be a potent cause, especiallyinthe youngest exposed the PC that a given cancer is the result of a previous exposure; this is individuals,femalesbeingmoresensitivethanmales.Adolescentsare calculated by use of the following relationship: less sensitivethan youngerchildren.The relativeriskfollowingexternal irradiationisatleastthreetimesgreaterthanthatfollowingirradiation PC—R/(1+ A), by internal emitters. whereAistherelati@riskduetoradiationexposureandthespontaneous 1. Schneider AB, Recant w, Pinsky SM, Ryo UY, Bekerman c, Shore-Freedman riskis1. E. Radia@on-induced thyrcid carcinoma. clinical course and results oftherapy Patientsexposedto diagnosticandtherapeutic radiationare different in 296 patienta Ann Intern Med 1986;105:405-412. fromthe general populationto some degree. Because ofselectionfac 2. ShoreRE,WoodardED,PasternackBS,HempiemanLH.Radiationand host tors otherthan radiation, PC values based on radiation risk factors and factors in human thyroid tumors fciI@ing thymus irradiation. Health Phys 1980;38:451-465. (contlnusd on page 1215)

1182 The Journal of Nuclear Medicine•Vol.33 •No. 6 •June1992 rests. These relatively simple meas- the patient relatively stationary during a, so far, unavoidable but often toler ures usually, but not always, maintain transmission and emission measure able source of error. the patient probably within a centi ments, in addition to maintaining meter and/or a few degrees between alignment between emission and the transmission and emission meas transmission images. M.M. Ter-Pogossian urements. This has been verified at It is very useful to know the mag Washington University our institution in a number of cases nitude of the effect produced by mis St. Louis, Missouri by carrying our two blood-pool im alignment as a function of patient aging procedures before and after translations and/or rotations. With REFERENCE measurements to verify the correct proper care, these motions can be kept 1. Thompson Ci, Ranger N, Evans AC, Gjedde A. Validation of simultaneous PET emission and position ofthe patient. This approach to a minimum, under which circum transmission scans. J Nuci Med 1991;32:154— offers the added advantage of keeping stances the described effect introduces 160.

(continuedfrompage 1182) SELF-STUDY TEST ANSWERS

baselineratesin the generalpopulation would not apply. For instance, ITEMS 21-23: AdverseEffectsof32@Therapyof Polycythemia anorgantransplantpatientmaybeata muchgreaterrisk,asmuchas Vera 30 timeshigherinsome cases, forcancer duringhisor her lifetimecom ANSWERS: 21, F; 22, T 23, T pared with a typical member of the population. -32administeredas the phosphate in high doses to treat Becauseofthe establishedvariationin incidenceforspontaneousand polycythemiavera has the desired effect of decreasing the number of radiation-inducedcancer, PC tables must take into account both age circulating plateletsand erythrocytes.Leukopenia,predominantlylym and sex. Becausetobacco smoking (particularlycigarette smoking)is phopenia,is notedaswithanyotherhighwhole-bodyradiationexposure. the singlemostimportantexternalriskfactorforhumancancer,estimated Leukemiadoesoccur in increasedfrequencyinthesepatients,although to cause 25%_40% of all cancer deaths in the U.S., it is alsotakeninto it is not certain whether this is due to the radiation exposure per se or account. to the longer lifespan of 32P-treatedpatients,giving more time for the Theweightof radiobiologicalevidencefavorsa linear—quadraticdose naturalevolutiontoleukemiathatoccursinthis diease.Noelevatedmci response to low-LET radiation for most cancers. Thyroid cancer and dence ofthyroidcancerhasbeenreportedin patientswithpolycythemia female breastcancer are exceptionsin that the epidemiologic data for vera treated with 32@ these cancers strongly favor a linear dose response. Reference ITEMS 24-27: Therapywith RadlolabeledMonoclonalAntibodies 1_ Gur D, Wald N. Probability of causation tables and their possible implications ANSWERS:24, F: 25. F: 26. F: 27, F forthepracticeof radiologyRadiology1986:158:853-854. Radiolabeled monoclonal antibodies show great promise for use in diagnosis. However,the tumor-to-background ratios achieved with ITEMS 11—15:RIsks of 1311Therapy for Thyroid Carcinoma radiolabeledmonoclonalantibodiesgenerallyhavebeentoo lowto permit ANSWERS: 11, T; 12, 1@13, F; 14, F; 15, F useoftheseagentsasthe solemeansoftreatmentoftumor metastases. Edmondsand Smithhavereportedthefollow-up of258 patientstreated The radiosensitivityof the bone marrow usuallylimitsthe ability to ob with high doses of 131lfor thyroid cancer.They observed a small but tama fulltherapeuticeffect.Nonuniformdose distributionis due in part significant excess of deaths from cancer of the bladder and from to regionalbloodflowvariations,whichalongwithantigenicheterogeneity. leukemia. Despite the high levels of irradiation of the salivary glands, nonspecificityoftumor-associatedantigens,andchangingantigeniccom no malignanciesand only one adenoma were found. No evidence of positionoftumors,limmtthecurrentutilityof monoclonalantibodytherapy. reduced fertility or of overt genetic damage has been reported in in Becauseit is difficult to ensure that antibodies will bind to each cell of dividuals (and their offspring) treated with 131lfor thyroid cancer the tumor.the useof radmonuclidesemittingshort-range,high-LETradia References tions (e.g., alpha particles)is not optimal. Beta emissionis more likely 1. Edmonds CJ. Smith T The long-term hazards ofthe treatment ofthyroid cancer to result in a more uniform dose distribution within the tumor. with radioiodine. Br J Radio! 1986:59:45-51 References 2. SakarSD.BeierwaltesWH.GillSR CowleyBJ Subsequent fertilityand birlh 1 Carrasquillo JA. Krohn KA. Beaummer P et al Diagnosis and therapy for solid historiesofchildrenandadolescentstreatedwith1311forthyroidcancerJ Nuc! tumors with radmolabeledantibodies and immune fragments Cancer TreatRep Med 1976:17:460-464. 1984.68317-328 2 Grossman ZD. Rosebrough SF ClinicalRadioimmunoimaging Orlando. FL @ ITEMS 16-20: Adverse Effects of 131 Therapy for Thyroid Grune& Stratton.1988 Carcinoma 3 Maners AW.Sanders MM. Pappas AA Current status of radmoligandantibodies ANSWERS: 16, F; 17, T 18, F; 19, T, 20, F in the treatment of malignancy Ann C!in Lab Sc' 1988.1853-57 Undesirable side-effects of with internal emitters are 4 OrderSE Radmoimmunoglobulmntherapyofcancer Compr Ther1984.10 9-18 much less prominent than those encountered with external beam radia 5. Vaughan AT.Anderson P Dykes PW. Chapman CE. Bradwell AR Limitations tion therapyor chemotherapy.The parathyroidgland is rarelyclinically of the killing of tumours using radiolabelied antibodies Br J Radiol impaired by eventhe highest dose proceduresto the thyroid with 1311; 1987.60 567-578 only isolated cases of hypoparathyroidismhave been reported. The ITEMS 28-32: Dose-EquivalentConceptwith Bone Marrow limitingtissue dose is that to the bone marrow,which receivesapprox Exposure imately 0.5 /mCi of 131ladministered to the patient with thyroid cancer. Radiationnephritisis not a reportedcomplication of 131I therapy(or of ANSWERS: 28. T: 29, T: 30. F: 31. F: 32. F Thereiscontroversyregardingthecomparabilityof riskcoefficientsbased other nuclear medicinetherapy).Mild nauseamayoccur, but on partial-bodyradiationexposurewiththose basedon whole-bodyex is a rare complication (

MisalignmentBetween PETTransmission and EmissionScans •Ter-Pogossian 1215 Med l98627:1830—1836. ments for 3-dimensionalquantificationof myocardialfunctionwith posi 2. Garcia E, Van Train K. Maddahi J, et al. Quantification of rotational tron emissiontomography.IEEE TransNuc/Sci 1989;36:l030—1033. thallium-20l myocardial tomography. I NuciMed 1985;26:17—26. 9. SchaferR@,RabinerLW.A digitalsignalprocessingapproachtointer 3. O'Brien A, Gemmell H. Effectiveness of oblique section display in thaI polation. ProcIEEE 1973;61:692—702. lium-20l myocardialtomography.NuciMed Comm 1986;7:609—6l6. 10. Carter WH. Image sampling and interpolation. SPIE l983;397:477—486. 4. DePasquale E, Nody A, DePucy E, et a!. Quantitative rotational Tl-201 1 1. Keys RG. Cubic convolution interpolation for digital image processing. tomography for identifying and localizing coronary artery . Circu IEEE TransAcoust,Speech,SignalProcessing1981ASSP-29:1153—1160. Iaiion1988;77:316—327. 12. Macland E. On the comparison of interpolation methods. IEEE Trans 5. Tamaki N, Yonekura Y, Mukai T, et al. Segmentalanalysis of stress Med Imaging1988;7:213—217. thallium myocardial emission tomography for localization of coronary 13. Gambhir S. Quantitation ofthe physical factors affecting the tracer kinetic arterydisease. EurlNuclMed 1984;9:99—l05. modeling ofcardiac emission tomography data. PhD dissertation. 6. SendaM,YonekuraY,TamakiN,et al.Axialresolutionandthevalueof University ofCalifornia, Los Angeles 1990. the interpolatingscan in multislicepositroncomputedtomography.IEEE 14. BardY.Noniinearparamezerestimwion,1stedition.NewYork:Academic Trans Med Imaging 19854:44—51. Press;1974:341. 7. HicksK, Ganti G, Mullani N, Gould KL. Automatedquantitationof 15. Karp J, Muehllehner G, MankofFD, et al. Tomograph with volume three-dimensionalcardiacpositronemissiontomographyfor routine din imaging capability. I NuciMed l990;31:617-627. ical use.JNucIMed l989;30:l787—l797. 16. MullaniN, GouldK, HartzR, et al. Designandperformanceof posicam 8. RaylmanR, HutchinsG, SchwaigerM,ParadiseA.Axialsamplingrequire 6.5 BGO positroncamera.JNucIMed 1990;31:610—616.

(continued on page 1215) SELF-STUDY TEST ANSWERS

@ This concept is consistentwith the mean marrow dose,'‘which in i.e., preventit from spreading beyond the immediatearea of the spill. corporates a linear dose-response model (500 rads to 50% the mar The person who dropped the vial should have immediately placed row would have the same effect as 250 rads to 100% of the marrow). enough absorbent materialon the spill to soak up all of the liquid on Such an approach is clearly inconsistentwith a dose model that incor the floor.He or she shouldthen havecalled for assistanceand remain porates terms that are quadratic or otherwise nonlinear (the model ed in the areauntila surveymeterwasbroughtto check for contamina assumesthat 50 radsto 10% of an organ is equivalentto 5 radsto the tion of clothing and shoes.The second step should be stopping work wholeorgan—alinearextrapolation).Furthermore,if partial-bodydoses long enough to plan how best to proceed. Becausethe radiopharma are high enough to kill a significantnumber of cells, the hypothesisis ceuticalis not significantlyvolatile,so long as people are excludedfrom surely invalid. the contaminated area, there is no immediate hazard to anyone.The Thedose-equivalentconcept is not relatedto partialorgan irradiation, third step is to put on disposable foot covers,two pairs of disposable but provides a method of expressingall kinds of radiation exposures plasticgloves,and eithera laboratorycoat or a surgicalscrub suit.The on a common scale for calculating the effectiveabsorbed dose. fourth step is to quickly removeall of the broken glass and wet absor R•for•nc•s bent materialand place these into a heavy plastic bag or two nested 1 InternationalCommissionon RadiologicalProtectionRadiosensitivityaridSpa thin plastic bags; the plastic glovesshould be placed in the bag after fial Distribution of Dose, Publication 14.New York. Pergamon. 1969. all of the other debris has been picked up. The fifth step is to attempt 2 RosensteinM. OrganDoses in DiagnosticRadiology.U.S.Departmentof to removethe remaining superficial contaminationon the walls,cabi Health, Education, and Welfare, HEW Publication (FDA) 76-803. Washington. nets,and floor.All of thesecontaminatedmaterialsshould be removed D.C.: U.S. Government Printing Office, 1976. 3 ShleienB.TuckerTT,JohnsonDW.Themeanactivemarrowdosetotheadult fromtheclinicareaand placedinan approvedradioactivewastestorage populationof the UnitedStatesfrom diagnosticradiology.HealthPhys areaoverthe weekendfor decay.The dose ratein the area of the spill. 1978:34.587-601. which now will be substantiallylowerthan initially,should be reassess ed witha surveymeter.Atthis point mostradiationsafetyofficersproba ITEMS 33—36:Management of eemTcSpill bly would recommend labeling the area with the proper radioactive ANSWERS:33, T;34, F; 35, F; 36, F materialscautionsigns,cautioningnuclearmedicinepersonnelto avoid Theamountof99@―Tcspilled,20 GBq, isslightlymorethan 500 mCi.This the areaof the spillfor the remainderofthe day and overthe weekend. clearlyisa majorspill,and itcannotbe ignoredunderanycircumstances. and allowingthe 99mTcto decay overthe weekend. The contaminated The exposure rate constant for @mTcis approximately70 mR/hr/Ciat regions of the floor might also be covered with polyethylenesheeting 1 m, from which it can be calculated that the exposure rate at the dose to further reduce the likelihood of dissemination. preparationarea (4 m from a spill of 0.5Ci)will be on the order of about If the accident had occurred on Monday morning insteadof Friday 2 mR/hr.Thisisnotanalarminglyhighexposurerate,andworkinthis afternoon,thefirstfivestepsfor handlingthespillshouldbethesame. areacancontinueasnecessary.However,it wouldmostassuredlybe In fact,this would be true regardlessof the time of the weekor the acti inconsistentwith ALARA philosophyto ignorethe spilland to allowper vityof @9mTcinvolved.However,becausethe areawillbe occupied more sonnelto continueto work inthe areawithouteffortsto reduceexposure intensivelyduring the 24-48 hr necessaryfor 99Tcto decay,greaterat levels. tention must be paid to the dose ratefrom the residualcontamination Because of the large activity of 99Tcinvolvedand the relativelyhigh andto determinewhetheranyofthe residualcontaminationis removable . probability ofcontaminating large areas of the nuclear medicine clinic and might be disseminatedon individuals'shoesor clothing.The radia and hospitalifthe contaminationi@renotcontained,mostradiationsafety tion safetyofficershouldsurveythe laboratoryand makerecommenda officerswould agree that some decontaminationis necessary.The ac tions about avoidanceof the contaminatedareasor other adjustments tivity is not so large, however,that extraordinary precautions must be in work practices that will be required until the has decayed takenduring the clean-up.Thefirststepisto containthe contamination, completely.

For further in-depth information,refer to the syllabus pages in Nuclear Medicine Self-Study I.

1242 The Journal of Nuclear Medicine •Vol. 33 •No. 6 •June1992