11C-Raclopride的快速制备及生物学评价

摘要

Objective 11C-Raclopride is a type-2 dopamine receptor(D2R)binding agent used in the study of Parkinson's disease.This study introduced a fast and convenient method for preparation of 11C-Raclopride and reported on the preclinical trial of this receptor tracer on animal studies.Methods 11C-Raclopride was synthesized via reaction of 11C-CH3-Triflate with Nor-Raclopride.The mixture of primary product was water-diluted and loaded on Sep-Pak C18 column for separation.The final product,11C-Raclo-pride,Was purified by column chromatography and then eluted from the C18 column with ethanol.The bio-distribution was studied in SD rats and the in vivo imaging pattern was studied in hem ipark insonjan mon-keys.Results Within 16 min from beginning of processing with 11CO2,the synthetic yield of 11C-Raclo-pride WaS 60%,radiochemical purity(RCP)＞95% and specific activity 8 GBq/mmol.The uptake ratios of striatum to cerebellum and cerebral cortex were 4.67 and 6.20,respectively,at 30 min after 11C-Raclo-pride administration.The striatal uptake in normal rat brain could be blocked by N-methylspiperone(NMSP)and raclopride,but not by Nor-raclopride.PET imaging showed higher striatal D2 R uptake on the D2 receptor up-regulated side of the experimental monkeys relative to the contralateral side.Conclusions Column chromatography for purification of 11C-Raclopride Was fast,convenient and with a RCP similar to that of high performance liquid chromatography purification.Preliminary PET findings using animal model suggested that 11C-Raclopride by column chromatogram purification might be considered for clinical use.%目的 建立快速制备11C-雷氯必利(Raclopride)的方法,并对其进行生物学评价.方法 采用固相萃取法制备11C-Raclopride,即用11C-三氟甲基磺酰基甲烷(CH3-Triflate)与去甲基(Nor)-Raclopride反应得粗产品,用水稀释粗产品,将其转移到Sep-Pak C18反相柱,冲洗反相柱,再用乙醇淋洗得11C-Raclopride.研究正常SD大鼠体内11C-Raclopride分布,并行阻断剂(螺环哌啶酮)阻断后显像.制备食蟹猴帕金森病(PD)模型,行PET显像.结果 11C-Raclopride放化纯＞95%,比活度＞8 GBq/μmol,合成效率为60%,从11CO2到11C-Raclopride的合成时间为16 min.大鼠注射11C-Raclo pride 30 min后纹状体/小脑、纹状体/额叶皮质放射性摄取比值分别为4.67和6.20.Raclopride和螺环哌啶酮明显阻断了纹状体摄取11C-Raclopride,而Nor-Raclopride则不明显.PD模型猴11C-Raclo-pride PET显像示实验侧放射性高于对侧,出现D2受体上调.结论 固相萃取法制备11C-Raclopride速度快,放化纯高.动物显像表明11C-Raclopride能满足临床需求.