苯甲酰胺类多巴胺D2受体显像剂^18F-Fallypride的制备和生物分布

Preparation of dopamine D2 receptor imaging agent ^(18)F-Fallypride and biodistribution study in mice

以(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为氟标记前体,用K222催化进行氟标记,合成了(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)。考察标记物的放化纯度及稳定性,并进行ICR小鼠体内分布特性研究。结果显示,18F-Fallypride的放化产率为40.75%,合成时间40 min,放化纯度大于97%,标记物的生理盐水溶液室温放置4 h,放化纯大于95%。小鼠静脉注射18F-Fallypride后120 min,纹状体/小脑高达14.27。18F-Fallypride进入血液后很快被组织摄取,其中以肾的早期摄取最高(9.91±1.24)%ID.g-1,各脏器的清除均较快(T1/2<1 h),骨的摄取率随时间的延长而增加。

In this paper, we report preparation and biodistribution in mice of ^18F-Fallypride, a doparnine D2 receptor PET imaging agent. ^18F-Fallypride was prepared by nucleophilic fluorination of （s）-N-[（1-allyl-2-pyrrolidinyl）methyl] -5-（3-tolunesulfonyloxypropyl）-2,3-dimethoxybenzamide with K^18F/K222（Kryptofix） in a chemical process control unit. Purity and stability of the ^18F-Fallypride were checked by HPLC and TLC, the dynamic distribution in brain and critical organs of ICR mice were studied. The radiolabelling yield of ^18F-Faliypride was 40.75% and the radiochemistry purity was over 97%. The whole process （including synthesis, purification and analysis） took only 40 minutes. After 4 hours in room temperature, the radiochemical purity of ^18F-Fallypride was still over 95%. The striatum uptake was good, the striatum/cerebellum ratio reached 14.27 at 120 min. Among the critical organs, kidney had the first and the highest uptake （9.91±1.24 %ID·g^-1）. All organs had quick clearance （T1/2〈l h）. The radioactivity in bone increased with time. The results show that ^18F-Fallypride has a high striatum uptake and a high striatum/ cerebellum ratio, ^18F-Fallypride is a good dopamine D2 receptor agent. The autosynthesis method of ^18F-Fallypride is simple and fast with high labeling yield and high radiochemical purity. This method is fit for clinic use.