一种潜在5-HT_(1A)脑受体显像剂^(99)Tc^m-Bicine/HYNIC-MPP2的制备及其生物性能  

Preparation and Bio-Evaluation of ^(99)Tc^m-Bicine/HYNIC-MPP2 as a Novel Agent for 5-HT_(1A) Receptor Imaging

作　　者：张现忠[1] 庞燕[1] 范卫卫[1] 张俊波[1] 唐志刚[1] 

机构地区：[1]放射性药物教育部重点实验室北京师范大学化学学院,北京100875

出　　处：《核化学与放射化学》2009年第4期206-211,共6页Journal of Nuclear and Radiochemistry

基　　金：国家自然科学基金资助项目(No.20401004)

摘　　要：优化合成了含有1-(2-甲氧基苯基)哌嗪(MPP)结构的配体2-(4-(2-甲氧基苯基)哌嗪基)乙胺-6-叔丁基氧羰基肼基吡啶-3-甲酸(HYNIC-MPP2)。在室温下以N,N-二(2-羟基乙基)氨基乙酸(Bicine)为共配体制备得到配合物99Tcm-Bicine/HYNIC-MPP2,其放射化学纯度大于95%,并且在6 h内保持稳定。脂水分配系数和电泳实验结果表明,该放射性标记配合物是水溶性和电中性的。正常小鼠体内生物分布实验结果表明,99Tcm-Bicine/HYNIC-MPP2有一定的脑摄取(注射后2 min时为0.31%ID/g)。脑区域分布及抑制实验显示,该配合物在5-HT1A受体含量丰富的海马组织有较高摄取(注射后2 min时为1.00%ID/g),而在受体含量低的小脑组织中摄取也低(注射后2 min时为0.63%ID/g)。抑制后,海马摄取降低较多(注射后2 min时为0.42%ID/g),而小脑摄取则无明显变化。抑制前后海马/小脑比值分别为1.59和0.89。由此可见该标记配合物与5-HT1A受体具有一定特异性结合,是一种新的潜在5-HT1A受体显像剂。The goal of this study is to develop a new ^99Tc^m-complex as a potential 5-HT1A receptor imaging agent. Ligand HYNIC-MPP2, containing the MPP moiety was synthesized and labeled with technetium-99m. The ^99Tc^m-Bicine/HYNIC-MPP2 complex was prepared in high yield （〉95% by TLC） with N, N-bis（2-hydroxyethyl）glycine （Bicine） as coligand at room temperature （RT） and it remained stable over 6 h at RT. ^99Tc^m-Bicine/HYNIC-MPP2 complex is neutral and hydrophilic, that were conformed by paper electrophoresis and octanol/water partition coefficient, respectively. In vivo biodistribution of ^99Tc^m-Bicine/HYNIC-MPP2 was investigated in normal mice. The result shows that this complex has moderate brain uptake （0.31%ID/g at 2 min post-injection（p, i. ））. The regional brain distribution and blocking studies show that its hippocampus uptake of ^99Tc^m-Bicine/HYNiC-MPP2 is the highest （1.00 %ID/ g at 2 min p. i. ）, while the cerebellum uptake is only 0.63%ID/g at 2 min p. i.. This is agreed with the distribution of 5-HT1A receptor in the brain. After blocking with 8-OH-DPAT, the uptake of hippocampus is decreased obviously （0.42%ID/g）, while the eerebellar uptake has no significant difference. The hippocampus/cerebellum uptake ratio is decreased from 1.59 to 0.89 after blocking. This result shows that ^99Tc^m-Bicine/HYNIC-MPP2 has specific binding to the 5-HT1A receptor and it can be developed as a potential 5-HT1A receptor imaging agent in the future.

关 键 词：5-HT1A受体 99Tcm 2-(4-(2-甲氧基苯基)哌嗪基)乙胺-6-叔丁基氧羰基肼基吡啶-3-甲酸(HYNIC-MPP2) 生物分布 

分 类 号：R817[医药卫生—影像医学与核医学]