多巴胺D2受体显像剂~(99)Tc~m-MBZM的合成及生物性能评价

134200011JournalofIsotopesVol.13No.4Nov.2000D299Tcm-MBZM,,,(,102413):(Sulpiride),5()(S)2(-)2522N2[(12222)]222[MBZM]3+1(),D299Tcm2MBZM,99Tcm2MBZM,30min0.444%IDög;,30min2.1482.184%IDög;,2min0.145%IDög99Tcm2MBZM:D2;CNS;99Tcm;99Tcm2MBZM:O61417+12;R81714:A:100027512(2000)0420193206(CentralNervousSystem,CNS)(ö),CNS,99Tcm,99Tcm2TRODAT21,99TcmCNSö(),[1,2](Benzamide),D2,[3,4](Sulpiride),99Tcm,1111(SnCl22H2O):98%,Aldrich;(SodiumGluconate):98%,;(Sn2GH):;99Mo299Tcm:;:2000208216;:2000210220:(ContractNo.9104):(1966),(),,,©1994-2006ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(5Lm,U4.6mm250mm)Sep2PakC18(ClassicalCartridges):Waters;ITLC2SG:GelmanSciences;WhatmanNo.1:Whatman112LB2852:EG&G,Berthold;(WatersM250Model1510):Waters;LB506C21HPLC:Berthold;METTLERATORIONSA720pH:2211(MBZM)ReO(MBZM)(SNS)[5]N22(22)(SNS)(S)2(-)2522N2[(12222)]222(MBZM)ReO(MBZM)(SNS)212MBZM99Tcm2.2.1(Gluconate)(GH)99Tcm10mL,200LL100göL10LL10göL(SnCl22H2O),0.51mL99TcmO4-(370740MBq),,10min,99Tcm2Gluconate,,,99Tcm2GH,2.2.299Tcm2MBZM10mL,1mgMBZM0.5mgSNS10mg,pH,0.5mL99Tcm2Gluconate99Tcm2GH,,10min,99Tcm2MBZM213(SPE):Sep2PakC185mL5mL5mL,99Tcm2MBZM,5mL(10mmolöL,pH6.5)5mL80%,,1mL,HPLC99Tcm2MBZM214ShakingFlask100LLHPLC99Tcm2MBZM11ö(100mmolöL,pH7.4),(22)3min,20min,()(310LL),PP,3,PpH7.0pH7.22152.5.1(22)2.399Tcm2MBZMN2,49113©1994-2006ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(22),,HPLC2.5.299Tcm2MBZM(2.5.1)0.2mL(100mmolöLpH7.0,1100),37,510204060min,,,HPLC2.5.3L20.010.11.0mmolöLL2(100mmolöL,pH7.0)99Tcm2MBZM(2.5.1)L2,,37,510204060min,HPLC216SD,180200g3,0.2mL(200kBq)99Tcm2MBZM(HPLC),,,C,(%IDög)331199Tcm-MBZM99Tcm2MBZM1,HPLC21,Sep2PakC18,99Tcm2MBZM79mL3mL2HPLC99%ReTc,ReO(MBZM)(SNS)99Tcm2MBZM,99Tcm2MBZMReO(MBZM)(SNS)199Tcm-MBZMSep-PakC185914:D299Tcm2MBZM©1994-2006ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.(a)(b)2HPLC:WatersSpherisorbODS2,5Lm,U4.6mm250mm,:V(10mmolöL,pH6.5)V()=4555,1mLömina:UV(K=254nm),ReO(MBZM)(SNS);b:C,99Tcm2MBZM31299Tcm-MBZM1CONHPyrrolidinyl(MBZM)CH3N(SNS),pH,,pHP(lgP)199Tcm-MBZM(22)pHPlgP7.03.2140.5077.24.4630.6487.45.4730.73831399Tcm-MBZM399Tcm2MBZM()7h,99Tcm2MBZM(37)60min3,99Tcm2MBZM0.01mmolöLL2,3760min,0.1mmolöL1.0mmolöL,99Tcm2MBZMMBZM,[6]69113©1994-2006ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.ög;,30min2.1482.184%IDög;,99Tcm2MBZM,2min0.145%IDög,,(),99Tcm2MBZMReO(MBZM)(SNS)[3H]2spiperone,IC50Ki6.24910-7molöL1.23510-7molöLRe(V)O3+ReO(MBZM(SNS))D2399Tcm-MBZM+;,,0101,011,110mmolöLL2;,,,0101,011,110mmolöL299Tcm-MBZM(xqs,n=3)öID%ög2min5min15min30min3.3121.3701.0640.0380.5060.0750.4440.1191.9060.5461.3030.3100.8390.1720.7680.0170.6130.0751.9860.2601.7430.1042.1480.2570.7730.2211.7340.9361.2810.2201.2420.3870.7440.1253.3430.0782.5440.1802.1840.4500.1450.0020.0800.0040.0720.0030.0720.0237914:D299Tcm2MBZM©1994-2006ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.:[1]KungHF,KimHJ,KungMP,etal.ImagingofDopamineTransporterinHumansWithTechnetium299mTRODAT21[J].EurJNuclMed,1996,23:15271530.[2],,,.99Tcm[J].,1998,11:184188.[3]dePaulisT,KumarY,JohansonL,etal.PotentialNeurolepticAgents.4.Chemistry,BehavioralPharmacology,AndInhibitionof[3H]spiperoneBindingof3,52disubstitutedN2[(12ethyl222pyrrolidinyl)methoxy]262methoxy2salicylAmides[J].JMedChem,1986,29:6169.[4],,,.D2[J]1,1995,18:6516541[5]HuJi,HeYoufeng,WangYishang,etal.DesignandSynthesisofNewNeutralRe(V)OComplexDerivedFromBenzamide[A].ConferenceHandbook&AbstractsintheThirdInternationalConferenceofIsotopes[C]1Vancouver,Canada1September610,19991C1.2.[6]SyhreR,SeifertH,SpiesA,etal.StabilityVersusReactivityof3+1Mixed2ligandTechnetium299mComplexesinVitroandinVivo[J].EurJNuclMed,1998,25:793796.SynthesisandBiologicalEvaluationof99TcmLabeledBenzamidesforDopamineD2ReceptorImagingHUJi,HEYou2feng,WANGYi2shang,XIAOLun(DepartmentofIsotopes,ChinaInstituteofAtomicEnergy,Beijing102413,China)Abstract:(S)2(-)252mercapto2N2((12ethyl222pyrrolidinyl)methyl)222methoxybenz2amide[MBZM]issynthesizedbyintroducingamercaptogroupat52positionofbenzeneringtomimicsulpirideligand.Throughthe3+1mixedligandapproach,aneutralradiolabeledcompound99Tcm2MBZMisalsopreparedasapotentialD2receptorimagingagent.99Tcm2MBZMexhibitesafastclearanceinbloodandhigheruptakeintheliverandkidney(2.148and2.184%IDögat30minrespectively)butlowinitialbrainuptake(only0.145%IDögat2min).Theresultspreclude99Tcm2MBZMfrommakingabrainreceptoragent.Keywords:D2receptor;CNSreceptorimaging;99Tcmlabeling;99Tcm2MBZM89113©1994-2006ChinaAcademicJournalElectronicPublishingHouse.Allrightsreserved.