多巴胺D2受体显像剂^(99)Tc^m-MBZM的合成及生物性能评价

Synthesis and Biological Evaluation of ^(99)Tc^m Labeled Benzamides for Dopamine D2 Receptor Imaging

本工作以舒必利 (Sulpiride)为分子模型 ,在芳环的 5位上引入巯基 (替代磺酰胺基 )合成了 (S) -(- ) - 5-巯基 - N- [(1 -乙基 - 2 -吡咯烷基 )甲基 ] - 2 -甲氧基苯甲酰胺 [简写为 MBZM ]左旋异构体。通过“3+1”(二元混合配体络合 )方案 ,合成了一种新的 D2受体显像剂 99Tcm - MBZM。其在大鼠体内的生物分布实验结果显示 ,99Tcm- MBZM在血液中的清除较快 ,30 min后降到 0 .444% ID/ g;在肝和肾脏中的放射性则持续较高 ,30 min后仍分别达 2 .1 4 8和 2 .1 84% ID/ g;在脑中的摄取量偏低 ,2 min时仅为 0 .1 4 5 % ID/ g。因此 99Tcm - MBZM不能作为脑受体显像剂。

S) (-) 5 mercapto N ((1 ethyl 2 pyrrolidinyl)methyl) 2 methoxy benz amide [MBZM] is synthesized by introducing a mercapto group at 5 position of benzene ring to mimic sulpiride ligand.Through the “3+1”mixed ligand approach, a neutral radiolabeled compound 99 Tc m MBZM is also prepared as a potential D2 receptor imaging agent. 99 Tc m MBZM exhibites a fast clearance in blood and higher uptake in the liver and kidney (2.148 and 2.184 %ID/g at 30 min respectively) but low initial brain uptake (only 0.145 %ID/g at 2 min).The results preclude 99 Tc m MBZM from making a brain receptor agent.