一种潜在5-HT1A脑受体显像剂99Tcm-Bicine/HYNIC-MPP2的制备及其生物性能

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~(99)Tc~m-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,~(99)Tc~m-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-HT_(1A)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-HT_(1A)受体具有一定特异性结合,是一种新的潜在5-HT_(1A)受体显像剂.

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

The goal of this study is to develop a new ~(99)Tc~m-complex as a potential 5-HT_(1A) receptor imaging agent. Ligand HYNIC-MPP2, containing the MPP moiety was synthesized and labeled with technetium-99m. The ~(99)Tc~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. ~(99)Tc~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 ~(99)Tc~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 ~(99)Tc~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-HT_(1A)receptor in the brain. After blocking with 8-OH-DPAT, the uptake of hippocampus is decreased obviously (0.42%ID/g), while the cerebellar uptake has no significant difference. The hippocampus/cerebellum uptake ratio is decreased from 1.59 to 0.89 after blocking. This result shows that ~(99)Tc~m-Bicine/HYNIC-MPP2 has specific binding to the 5-HT_(1A) receptor and it can be developed as a potential 5-HT1A receptor imaging agent in the future.