18F-Fallypride的自动化合成与小动物PET显像

目的 研究高效、简单的自动化合成多巴胺D2受体显像剂(S)-(-)-N-(1-烯丙基吡咯烷-2-氨基甲基)-5-(3-18F)-2,3-二甲氧基苯甲酰胺(18F-Fallypride)的方法,并用小动物PET观察其在小鼠活体内的生物分布.方法 采用国产氟标记多功能模块控制整个过程,18F-在乙腈溶液中与前体(s)-(-)-N-(1-烯丙基吡咯烷-2-氨基甲基)-5-(3-磺酰基)-2,3-二甲氧基苯甲酰胺(OTSF)直接反应生成18F-Fallypride,混合物装柱,产品被C18柱吸附,用水冲洗柱,用少量乙醇淋出,加生理盐水稀释.ICR小鼠给药后经小动物PET活体显像.结果 18F-Fallypride放化产率为40.7%(已校正),合成时间为40 min,无需高效液相色谱(HPLC)法分离,放化纯＞95%.注射18F-Fallypride后ICR小鼠经小动物PET显像,脑内纹状体区域摄取最高,且双侧放射性浓聚对称,清除较慢.结论 18F-Fallypride自动化合成速度快,效率高.18F-Fallypride适于多巴胺D2受体显像.

Synthesis and small-animal PET image of 18F-Fallypride

Objective Benzamide,5-(3-fluoropropyl)-2,3-dimethoxy-N-(2S)-1-(2-propenyl)-2-pyrrolidinyl]methyl(Fallypride)is a well-known dopamine D2 and D3 antagonist.18F-Fallypride PET has been used to study D2 and D3 receptor occupancy and density in neuropsychiatric disorders and aging in humans.This study aimed to develop an automated synthesis of the potent dopamine D2 and D3 receptor PET imaging agent and to study the distribution of the mice by small-animal PET.Methods 18F ion Was reacted with precursor(s)-(-)-N-(1-allyl-2-pyrrolidinyl)methyl-5-(3-tolunesulfonyloxypropyl)-2,3-dimethoxy-benzamide in a chemical process control unit(CPCU).The crude product was transported to a C18 column.18F-Fallypride was absorbed on the column.the column Was washed by water.18F-Fallypride was then eluted from the column with small volume of ethanol.The mice were imaged by small-animal PET after in travenous 18F-Fallypride(1.85 MBq).Results It took 40 min for synthesizing 18F-Fallypride at CPCU,the radiochemical yield was 40.7%(end of synthesis),and the radiochemistry purity Was over 95%.Higher accumulation and delayed clearance of the 18F-Fallypride at bilateral striata was noted in imaging mouse brain with small-animal PET.Conclusions An optimal yielding of 18F-Fallypride at CPCU could be obtained.18F-Fallypride could demonstrate dopamine D2 and D3 receptor at mouse brain.