标记及生物分布研究

234Vol.23No.4200111JournalofNuclearandRadiochemistryNov.2001:2000209201;:2001208209:(2973102021):(1972-),,,,:025329950(2001)042020320899TcmD2,,,,,(,100875):3D2:N2[(22)]22,32(MEDM2BZM),N2[(22)]25222,32(MEBDM2BZM),N2[(22)]232(MEE2BZM),3221,523+199Tcm,85%3:D2;;;99Tcm:O615142:A,(DopamineReceptorSystem),(,)[1,2],11C,18F,123ID2,IBZM[3],FULLYPRIDE[4]99Tcm,,,99Tcm99Tcm,52HTBRANDAN[5],H.SPIES[6],H.F.KUNG[7,8]D299Tcm,99Tcm,(B.B.B.),,99Tcm,99Tcm,[9],D2,,(integratedmethod),99Tcm,,99TcmD2,D299Tcm1111,,;,,;,,;,,SIGMA,,,;,,;32,;3221,52(SSS),,ALDRICH;GH,Necolet2170SX;Avance500MHz,BRUKER;TRACEGC2MS,FINNIGAN112:112112,32[10],4750,60%40223112122,32[11],124127,67%112135222,32[12],8081,3516%11214MEDM2BZM25mL,014g(2.4mmol)2,324(DMF),017mL(9.83mmol),651h,,,25mL,012g(2mmol)0.72mL(6mmol),10min10mL,,24h,1mol/L3,35mL,,V(CH2Cl2)V(CH2OH)=101,,Rf=0.25IR(KBr):CONH=1667cm-1;1HNMR(D2O)():21942198(m,2H),3.793.85(m,2H),3.894.09(m,6H),7.037.12(m,1H),7.157.26(s,1H),7.687.70(s,1H);MS(FAB+,m/z)24211215MEBDM2BZM5222,32,11214,V()V()=11,,Rf=0.4IR(KBr),CONH=1667cm-1;1HNMR(D2O)():21752.82(m,2H),3.273.32(m,2H),3.613.82(m,6H),7.137.16(s,1H),7.817.82(s,1H);MS(FAB+,m/z):32011216MEE2BZM32,11214,V()V()=101,,Rf=0.2IR(KBr),CONH=1667cm-1;1HNMR(D2O)():11421144(m,3H),2.773.00(m,2H),3.623.80(m,2H),3.994.11(m,2H),7.017.05(s,1H),7.267.39(m,3H);MS(FAB+,m/z):22611399Tcm11311GH99Tcm1815MBq,304010min100g,pH=5.06.0,99Tcm2GH,7010min,:11312GH,5024:99TcmD2,,,99Tcm2GHRf=018110;99TcmO4-Rf=0011;99TcmO2xH2ORf=0011:V()V()=101,,,Rf=0.00.1,,Rf=017110,Rf=010011,85%114011mL99Tcm(L)(SSS)pH710,714011mol/L2,,,lgP1151820g12,011mL(0174MBq),2,15,30,60min,(ID/(%g-1))221121111pHpH311,pH=56,1pHTable1InfluenceofpHvalueonthelabelingyield%pH(ligands)315318411416511610614711715810815MEDM2BZM591681159611911688148516MEE2BZM611987119011681269166115MEBDM2BZM5812621491198518821279142111210min,22,,70,310min2Table2Influenceofreactiontemperatureonthelabelingyield%(ligands)t/20304050607080MEDM2BZM8019811388148919901994119016MEBDM2BZM6817751478128311841289178416MEE2BZM7914801081198311871390118210211133360223,75g,,75100g3Table3Influenceofligandquantityonlabelingyield%(ligands)m/g255075100150200250MEDM2BZM8810881392118819881387118819MEBDM2BZM8810871390169016891790188910MEE2BZM681971117717821681178317-2111444,10min,10min4Table4Influenceofreactiontimeonlabelingyield%(ligands)t/min510152030MEDM2BZM82118712861586148515MEBDM2BZM89199111901691169115MEE2BZM77198314821483128216,,,011mL2%802,,21235,3,pH,lgP5Table5ThelgPvalueofcomplexes(complexes)pH=710pH=71499Tcm(MEDM2BZM)(SSS)1.191.1999Tcm(MEBDM2BZM)(SSS)1115113099Tcm(MEE2BZM)(SSS)1117112921399Tcm(L)(SSS)68,37024:99TcmD2,99Tcm(MEBDM2BZM)(SSS),99Tcm(MEDM2BZM)(SSS)99Tcm(MEBDM2BZM)(SSS)2min,0179%/g,1108%/g,1117%/g;699Tcm(MEBDM2BZM)(SSS)Table6Biodistributionof99Tcm(MEBDM2BZM)(SSS)inmice%/g(tissues)2min15min30min60min(blood)161641115419201252187013421460138(heart)61300139219501011190010611830135(lung)311263134211760108201310172161002159(kidney)10104018961290132515401015151015(liver)341910171371161149351132144311713106(brain)01790116013901030126010101250104(note):n=3799Tcm(MEDM2BZM)(SSS)Table7Biodistributionof99Tcm(MEDM2BZM)(SSS)inmice%/g(tissues)2min15min30min60min(blood)91820180319301263175017921400126(heart)81551118514511066116210941270127(lung)1212101911112321439125112871170136(kidney)91053162617901165167015241440137(liver)191913198221142138191800193131942144(brain)11080112018101100178010601670105(note):n=3899Tcm(MEE2BZM)(SSS)Table8Biodistributionof99Tcm(MEE2BZM)(SSS)inmice%/g(tissues)2min15min30min60min(blood)111160134713311895172011751510138(heart)41840143313601543103012021980108(lung)181541180131470192111121101141441168(kidney)61330136416501514112013351281164(liver)131720146131031114131140105141825174(brain)11170101017701061102012501490112(note):n=38022333D2,3221,523+199Tcm,85%3,:[1]KUNGHF.RadiopharmaceuticalsforCNSReceptorImagingWithSPECT[J].NuclMedBiol,1990,17(1):85.[2]CHUMPRADITS,KUNGMP,KUNGHF.FluorinatedandIodinatedDopamineAgents(FIDA):D2ImagingAgentsforPETandSPECT.9thinternationalSymposiumonRadiopharmaceuticalChemistry.6210thApril(1992),Abstracts:23.[3]KUNGHF,BILLINGSSJJ,GUOYZ,etal.Preparationandbiodistributionof[125I]IBZM:APotentialCNSD2DopamineReceptorImagingAgent[J].NuclMedBiol2IntJRadApplInstPartB,1988,15:195.[4]MUKHERJEEJ,YANGZY,DASMK,etal.FluorinatedBenzamideNeuroleptics.Developmentof(S)2N2[(12ally222pyrrolidinyl)methyl]252(32[18F]fluoropropyl)22,32dimethoxy2benzamideasanImprovedDopamineD2ReceptorTracer[J].NuclMedBiol,1995,22:283.[5]SAMNICKS,BRANDAUW,SCIUKJ.Synthesis,CharacterizationandBiodistributionofNeutralandLipid2Soluble99Tcm2BisaminoethanethiolSpiperoneDerivatives:PossibleLigandsforReceptorImagingWithSpect[J].NuclMedBiol,1995,22(5):573.[6]SPIESH,NOLLB,NOLLST,etal.Derivativesof62Methyl282amino2ergoline:SynthesisandAffinitytotheDopamineD2Receptor[J].QJNuclMed,1998,42,Suppl.13:22.[7]CHURNPRADITS,KUNGMP,PLOSSLK.DesignandSynthesisof99Tcm2LabeledBenzamidesasPoten2tialDopamineD2/D3ReceptorImagingAgents[J].QJNuclMed,1998,42,Suppl.13:30.[8]CHUMPRADITS,KU