^11C-Raclopride的快速制备及生物学评价  

Fast synthesis of ^11C-Raclopride and its initial PET study on animal model

作　　者：张锦明[1] 田嘉禾[1] 姚树林[1] 丁为民[1] 尹大一[1] 刘伯里[2] 

机构地区：[1]解放军总医院核医学科,北京100853 [2]北京师范大学化学学院

出　　处：《中华核医学杂志》2008年第4期227-230,共4页Chinese Journal of Nuclear Medicine

基　　金：全军“十五”课题项目（01MA120）;国家“863”重大课题项目（2002AA205081）

摘　　要：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-Raclopfide，即用^11C-三氟甲基磺酰基甲烷（CH3-Triflate）与去甲基（Nor）-Raclopnde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-Raclopfide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〉8GBq／umol，合成效率为60％，从^11CO2到^11C-Raclopride的合成时间为16min。大鼠注射^11C-Raclopride 30min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-Raclopride 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-Raclopfide能满足临床需求。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 ^11 C- 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 monkeys. Results Within 16 min from beginning of processing with ^11CO2 , the synthetic yield of ^11C-Raclopride 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-Raclopride 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 D2R 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.

关 键 词：雷氯必利 同位素标记 碳放射性同位素 受体 多巴胺 动物 实验 

分 类 号：R686[医药卫生—骨科学]