radionuclidetherapy放射性治疗课件

RADIONUCLIDETHERAPY1Easilypreparedorreadilyavailable2Stableinvivobindingofradionuclidetopharmaceutical3Minimalnon-specificuptake4Hightumoraccumulation5Longtumorresidencetime6CheapCharacteristicsofanidealtherapeuticradiopharmaceuticalRadiopharmaceuticalTumor1131IFollicular/papillary;ThyroidcarcinomaMixedthyroidCarcinoma289SrCl2;153SmSkeletalMetastases390Y-microspheresBone;Liver490Y-McAbOvarian590Y-McAbOvarian;Melanoma6131I-MIBGNeuroblastoma;Paraganglioma;MedullarythyroidcarcinomaRadiopharmaceuticalsintherapyContentsRadioiodinetherapyofhyperthyroidismRadioiodinetherapyofthyroidcarcinomaRadionuclidetherapyofbonemetastasisHyperthyroidismcansimplybedefinedasahypermetabolicstateinducedbyexcessthyroidhormone.Itcandevelopsecondarytothyroidhormonereleasedfromover-activeorinflamedthyroidglandorintroducefromanextraglandularsource.Thecommoncauseofhyperthyroidismincludestoxicdiffusegoiter(Gravesdisease).autonomousfunctioningnodulargoiter(Plummerdisease).1.RadioiodineTherapyofHyperthyroidismThetherapeuticapproachestohyperthyroidismareablationofperipheraltissueblockadeofnewhormonesynthesisinhibitionoftheperipheraleffectsofthehormoneand/orconversionofT4toT3.Treatmentmodalitiesincluderadioiodine,drugtherapy(thionamides,iodine,andbetablockers),andsurgery.Theactualtherapyselectedonthecharacteristicsoftheindividualpatientandtheunderlyingcauseofhyperthyroidism.Thecomparisonofhyperthyroidismin3kindsoftreatmentsDrugsSurgeryRadioiodineRelapseorrecurrenceHighLowLow(dose-related)hypothyroidismLowIntermediateIntermediate(dose-related)EaseoftreatmentandcostIntermediateLeastfavourableSimpleandcheapComplicationsRareLowbutsignificantmortalityandmorbidityRareOnsetoftherapeuticeffectModerate(1or2weeks)RapidafterSurgerySlow(fewweeks)Iodine-131istheonlyradioisotopestillusedforthetherapyofthyroiddisease.Itablatesthyroidtissuebyselectivelylocalizinginhyperfunctioningthyroidtissue.Theiodineatomisactivelytrappedandorganifiedontotyrosinecontainedinintrathyrodialthyroglobulin.Iodine-131emitsabetaparticlewithmeanenergyof0.19Mev(macimum,0.81Mev),anaveragepathrangeof0.8to1mm.1.1PrincipleWheniodine-131localizedinhyperfunctioningcells,betaparticlecanalterordestroycell,finallycausefocalfibrosisbyresultingfromionizationandexcitationofnuclearDNA.Thereby,aimtodestroyenoughhyperfunctioningthyroidtissueandrestoretoeuthyroidism.

1.2Indication1.PatientswhoareGrave’sdiseasewithmoderatesymptomandsigns,ageabove25years.2.Patientswhoarepoorsurgicalrisksorrefusetooperation.3.Patientswhohaverecurrencefollowingsurgicalormedicaltherapy.4.Patientswhoarenoteffectorallergictoantithyroiddrugs.5.Patientswhoseeffectivehalftimeof131Iinthyroidisover3days.1.Patientswhohaveseverehyperthyroidism.2.Patientswhoseleucocytecountisbelow3.0×109/L,orPltcount80×109/L3.Patientswhoseeffectivehalftimeof131Iinthyroidislessthan3ds.1.3RelativeContraindication1.PatientswhoareinpregnancyandLactation2.Patientswhohavelargegoiterwithpresssyndromeandsign3.Patientswhohaveseverehepaticandrenalinsufficiency4.Patientswhohavehyperthyroidismcomplicatedwithrecentmyocardialinfarction1.4AbsoluteContraindicationPatientPreparation1.Patientsshoulddiscontinueiodinecontainingdrugandfoodaffectingthethyroiduptakebeforetreatment,sameastheRAIU.2.PatientsshouldundergoRAIUtestanddeterminetheeffectiveT1/2of131I.3.Estimatetheweightofthethyroidglandusuallybypalpation(ormoreaccuratelybyultrasound).4.Patientscanbetreatedwithbetareceptorblockersifnecessary.1.5MethodTheselectionofanappropriatedoseof131Iisessentialtoavoidundertreatment(resultinginpersistentorrecurrenthyperthyroidism)orovertreatment(whichcanprogresstopermanenthypothyroidism).Thefollowingformulaisconvenientfordosecalculation.131I(μCi)=(estimatedweightofthyroidglandingrams×100μCi/g)/(MAX%uptakeofthyroid)Theselectionof100μCi/gisbasedonanestimateofthedesiredabsorbedradiationdose.Iodine131Imaybegiveninliquidorcapsuleform.Thetraditionalapproachadvocatestheadministrationof7000to10000radtothethyroid.

SelectionofTherapeuticDoseOtherfactorsaffectingtheefficacyofthisdoseincludethethyroidbiologichalftimeof131I,whichcanchangewithdrugsordiet,andtheradiationsensitivityofthethyroidgland,whichcannotbereadilyestimated.Ifitrequiresasecond,third,ormoredoses,retreatmentshouldnotbeconsideredforatleast6months.1.6AdverseReactionDuringearlyperiodof131Itreatment,therearenosignificantsideeffects.Sometimesjustamildgastrointestinalreaction,andnospecialtreatmentisrequired.ItisgenerallyacceptedthathypothyroidismisinevitableinpatientswithGravesdiseasetreatedwith131I.

Variousstudieshaveshownthatpatientsbecamehypothyroid1yearaftertreatmentandthattheincidenceofhypothyroidismisapproximately3%to5%eachyear.Butdelayedhypothyroidismdevelopsatthesamerate(after1year)regardlessofinitialdose.Withourpresentinabilitytopredictwhenhypothyroidismwilloccure,itiscrucialthatthepatientreceivesannualposttreatmentfollow-upsothathypothyroidismcanbereadilydiagnosedandtreated.Fiftyyearsofexperiencewith131Itreatmenthasshownnoincreaseintheincidenceofthyroidcancer,leukemia,orothermalignancies.Noprovedadversegeneticdefectshavebeennotedinchildrenwhoseparentspreviouslyweretreatedwith131I.1.7EvaluationofTherapeuticEffectIngeneral,therewasnoclinicalresponsefor3to4weeksafter131Itreatment.Themaximumeffectisusuallyseenin3to4months.Thepatientsmaybeseentheimprovementofsymptomandsign,whichincludethefallofT3andT4levelinserum.Inordertoobtainmorerapidcontrol,adjunctivedrugadministrationmaybeused,forexample,propranolol40mgq.i.d.80%-90%ofpatientsnolongerhavehyperthyroidismafterasingledose.

ThyroidcarcinomasareclassifiedbytheWorldHealthOrganizationaspapillary(70%to80%),follicular(15%),medullary(5%to10%),andundifferentiatedoranaplastic(5%).Well-differentiatedpapillaryandfollicularcarcinomasareslow-growingandcarryarelativelygoodprognosis.2RadioiodineTherapyofThyroidCarcinoma

Whilepoorlydifferentiatedmedullaryandanaplasticcarcinomasareaggressivewithapoorprognosis.Papillarycarcinomasaremorelikelytobefoundinregionalnodesthanfollicularcarcinomas,butfolliculartumorsaremoreoftendistantlymetastaticthanpapillarycarcinoma.2.1AblationofNormalThyroidGlandRemnantFollowingtotalthyroidectomy,onemustascertainthattherearenothyroidtissueremnantsaftersurgeryandthattherearenooccultmetastases.ImplicationofAblationofResidualTissueThyroidcancertendstobemultifocal,andanyremnantsofthethyroidglandcouldcontainmalignancyOcculttumormaybefoundandkilledwithanablationdoseIfoneremovesallfunctioningtissue,onecanuseserumthyroglobulinlevellaterasadiagnostictesttomonitorrecurrenceNormalthyroidtissuehasasignificantlygreateraffinityforiodinethanfunctioningthyroidcarcinoma,andsodetectionandtreatmentofcarcinomaaredifficultaslongasnormaltissueisallowedtopersistHormonesecretionbynormaltissueinhibitsendogenouspituitaryTSHstimulationof131Iuptakebytumor

IndicationIncludeallpatientswithwell-differentiatedthyroidcarcinomaandresidualpostsurgicalthyroidtissueortumorwithaffinityforiodine.Contraindication1.Patientswhoareinpregnancyandlactation2.Patientswhoarebelow3.0*109/Lofleucocytecountorwithseverehepaticandrenalinsufficiency3.Patientswhoarepoorlydifferentiatedthyroidcarcinomaorwithnoaffinityforiodineinfocus.MethodTheadministrationofthepostoperativediagnosticdoseof131Itodetectanythyroidremnantisperformed4to6weeksafterthyroidectomy,becauseatthistimetheserumTSHlevelexceeds30mIU,alevelthatstimulatesiodineuptakeinresidualthyroidtissue.Routinely,administeranablativedoseof100mCioradoseof150-250mCiwithdetectedfunctionalmetastasesinsomesites.Wholebody131Iscanperformed1-2weekafterablation.Onehasagreaterchanceofvisualizingfunctioningmetastasesaswellasremnantsofthethyroidgland.Ablationofresidualpostsurgicalthyroidglandortumorwith131Iisverydifficultifasignificantamountoffunctioningtissueremains.Furthermore,radiationthyroiditisisalikelyresult.Multiplesmalliodinedoseswouldberequiredoverarelativelylongtimetoavoidthiscomplication.Method2.2TreatmentofMetastaticThyroidCarcinomaIndicationPatientswithwell-differentiatedthyroidcarcinomawhohaverecurrenceandresidualpostsurgicaltumor,withaffinityforiodine.Patientswithwell-differentiatedthyroidcarcinomawhohavefunctionmetastaticfoci,withaffinityforiodine.Patientswithwell-differentiatedthyroidcarcinomawhohavefunctionmetastaticfoci,andcannotbeoperated.Contraindication1.Patientswhoareinpregnancyandlactation.2.Patientswhoseleucocytecountarebelow3.0×109/Lorwithseverehepaticandrenalinsufficiency.Selection

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Therapeutic

DoseThetreatmentforfunctioningmetastaticthyroidcarcinomamustbalancetheneedforacytocidaltumordoseagainstsideeffectsproducedinhealthytissuebysuchadose.Inadequatetreatmentcouldsimplyreducetheiodineconcentrationabilityofmetastases,reducingeffectivenessoffuturetherapy,withoutleadingtotumorsterilization.Whentheradiationdosetometastaticlesionsexceeded8000rads,98%oflesionsrespondedtotreatmentwhilenonerespondedtodoseslessthan3500rads.Ithasexcellentresultsusinganempiricallyadministeredactivityof150to175mCiforcervicalnodemetastase,175to200mCiforpulmonarymetastases,and200mCiforskeletalmetastaticdisease.Selection

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Therapeutic

DoseThisradioisotopeisoftensuppliedasasolutionofsodiumiodideand,especiallywithalowpH,isvolatile.Thereforethemanipulationof131Ishouldbeperformedinafumehoodwiththeexhaustfan.Alliodinevialsmustbehandledbehindleadglassshieldingwithlonghandletongs,andthenkeptinleadcontainers.

2.3RadiationSafetywithIodine-131Hospitalizedpatientsremaininasingleroomandaremonitoredonetotwotimesdailyforradiationburden,Savingurineforcountingpurposecanleadtocontaminatingspills.andthisisnotarecommendedsafetytechnique.Norestrictionsarerequiredwhentheaverageexposureratemeasures2mR/hratanydistance.2.3RadiationSafetywithIodine-1311.Cytopenia；2.Radiationpneumonitis；3.Acuteand/orchronicsialadenitis；4.Gastrointestinalradiationisnotuncommon,beginsabout4to12hoursafter131Iadministration,hasaprevalenceof50%to70%,andgenerallyresolvedby36hours,probablyrelatedtotheintestinalconcentrationof131I.2.4SideEffectof131ITherapyAutonomouslyfunctioningthyroidadenomaPre-therapyPost-treatmentBonemetastasisisacommonsequelaofsolidmalignanttumorssuchasprostate,breast,lungandrenalcancers,whichcanleadtovariouscomplications,includingfracture,hypercalcemia,andbonepain,aswellasreducedperformancestatusandqualityoflife.Theuseofconventionalradiographyandbonescanninghelpsconfirmthepresenceofbonemetastasisbutcanalsoassesstheextent.3.RadionuclideTherapyofBoneMetastasisClassifythelesionsintopredominantlyosteoblastic,ormixedtype;and,finally,Stratifythoselesionsthatareatriskforfractureorcordcompression.Thetreatmentofbonepainfrommetastasesremainpalliativeatpresent,andcanconsistofsystemicanalgesics,antitumoragents,hormones,chemotherapy,steroids,localsurgery,anesthesia,andexternalbeamradiation.3.RadionuclideTherapyofBoneMetastasisIngeneral,nosinglemethodwillkeepthepatientfreeofsymptomsforanextendedperiodoftime,andusuallyacombinationofsystemicandlocalmodalitiesmayberequired.Systemicallyadministeredradiopharmaceuticalsoffertheadvantageofwideapplicabilityinanoutpatientsetting.Injectionoftheradiopharmaceuticalsareeasilyadministeredwithouttheneedforexpensivehigh-technologyequipment.3.RadionuclideTherapyofBoneMetastasis3.1PrincipleandAgentsSeveralradiopharmaceuticalsfortreatingpainfulbonemetastaseshavebeendeveloped,Thephysicalcharacteristicsoftheseradionuclidesvary,andeachconferscertainbenefits.Mostoftheseagentsareadministeredintravenouslyandtargetthepainfulbonemetastsesbyaccretiontothereactivebonesiteswithahightargettonon-targettissueratioandaverylowconcentrationinthesurroundingnormalbone,underlyingbonemarrow,orotherstructure.Thecharacteristicsoftheemissions(β,internalconversion,orAugerelectrons)determinethetherapeuticsuitabilityoftheradionuclidebecausetherangeofpenetrationisrelatedtotheenergyoftheemittedparticles.Atpresent,radiopharmaceuticalforsystematicradioisotopetherapyincludeStrontium-89,Phosphorous-32,Samarium-153andsoon.3.1PrincipleandAgents3.2Indication1.Patientswhohavebonemetastasesprovedbyclinical,X-raysandskeletalimaging.Itisbetterformultifocibonemetastasisandbonemetastasisresultedfromprostate,breastandlung.2.Patientswhohaveseverebonepainresultedfrombonemetastasis.Othertreatmenthasnoeffect.3.Patientwhoareabove3.5×109/Lofleucocytecount,andPlt>80×109/L3.3

Contraindication1.Patientwhohaveosteolyticcoldregioninskeletalimaging.2.Patientwhoarebelow3.0×109/Lofleucocytecountorseverehepaticandrenalinsufficiency.3.4DoseSingleinjectionsofthesystemicradioisotope,givenover2-3min,reachallosteoblasticbonemetastases,regardlessofwhethertheyaresymptomaticorasymptomatic.Inadditiontotargetinglesionsthatarepredominantlyosteoblastic,theyalsotargetlesionsthataremixedandhavebothosteolyticandosteoblasticcomponents.Morethanhalfofthepatientswhoaretreatedobtainreliefofpain,thusreducingtheirneedforanalgesicsandimprovingthequalityoflifeandmobility.Reliefofpainmaybeachievedwithin2-7ddependingontheagentandmaylastseveralmonthsafterasingleinjection.3.4DoseSerialinjectionsmaybegivenifresponseispartialorifsymptomsreturnafterappropriaterecoveryofthebonemarrow,Thedoseof153Sm-EDTMPisfrom0.8to1.2mCi/kg.Thepatientsreceived30-40mCi/kgwith89Sr.Patientsreceiving2ormoredosesreceivedalittlemoredoseforallsubsequenttreatments.3.4Dose3.5EvaluationThegoalofsystemicradioisotopetherapyincludealleviatingpain;improvingthequalityoflife;decreasingtheamountofopioids,radiation,andchemotherapyused;andimprovingoutcomesandsurvival.Systemicradioisotopetherapymayreducetheoveralllong-termcostofpainpalliationwhileimprovingthequalityoflifeofcancerpatientswithbonepain.Futureconsiderationforsystemicmetabolicradi