【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。更多还原

【Abstract】 The goal of this study is to develop a new 99Tcm-complex as a potential 5-HT1A receptor imaging agent.Ligand HYNIC-MPP2,containing the MPP moiety was synthesized and labeled with technetium-99m.The 99Tcm-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.99Tcm-Bicine/HYNIC-MPP2 complex is neutral and hydrophilic,that were conformed by paper electrophoresis and octanol/water partition coefficient,respectively.In vivo biodistribution of 99Tcm-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 99Tcm-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 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 99Tcm-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.更多还原