Zhang Xianzhong, Zhou Panwang, Liu Jiaojiao, Huang Yan, Lin Yan, Chen Yanling, Gu Ting, Yang Wenjiang, Wang Xuebin
College of Chemistry, Beijing Normal University, Beijing, 100875, PR China.
Appl Radiat Isot. 2007 Mar;65(3):287-92. doi: 10.1016/j.apradiso.2006.09.001. Epub 2006 Oct 30.
The goal of this study is to develop a novel 5-HT(1A) receptor imaging agent. 4-[(2-methoxyphenyl)piperazin-1-yl]-dithioformate (MPPDTF) was labeled with (99m)Tc-tricarbonyl core via dithioformate moiety in high yield (>96% by HPLC). (99m)Tc(CO)(3)-MPPDTF is a neutral and lipophilic complex, which was confirmed by paper electrophoresis and octanol/water partition coefficient (P=27.0+/-1.4, n=3), respectively. In vivo biodistribution indicated that this complex had moderate brain uptake (0.53+/-0.10% ID/g at 5 min and 0.42+/-0.02% ID/g at 120 min) and good retention (about 80% of the activity was retained in the brain at 120 min post-injection). Regional brain distribution study showed that hippocampus, where the 5-HT(1A) receptor density is high, had the highest uptake (0.60+/-0.02% ID/g at 5 min p.i.) and the cerebellum, where the 5-HT(1A) receptor density is low, had the lowest uptake (0.10+/-0.02% ID/g at 5 min p.i.). After blocking with 8-OH-DPAT, the hippocampus uptake was decreased obviously while the cerebellum uptake was increased slightly. This result indicates that (99m)Tc(CO)(3)-MPPDTF complex has specific binding to 5-HT(1A) receptor.
本研究的目的是开发一种新型的5-HT(1A)受体显像剂。4-[(2-甲氧基苯基)哌嗪-1-基]-二硫代甲酸酯(MPPDTF)通过二硫代甲酸酯部分与(99m)Tc-三羰基核心进行标记，产率高(通过高效液相色谱法>96%)。(99m)Tc(CO)(3)-MPPDTF是一种中性亲脂性配合物，分别通过纸电泳和正辛醇/水分配系数(P=27.0±1.4，n=3)得到证实。体内生物分布表明，该配合物具有适度的脑摄取(5分钟时为0.53±0.10%ID/g，120分钟时为0.42±0.02%ID/g)和良好的滞留性(注射后120分钟时约80%的活性保留在脑中)。脑区分布研究表明，5-HT(1A)受体密度高的海马体摄取量最高(注射后5分钟时为0.60±0.02%ID/g)，而5-HT(1A)受体密度低的小脑摄取量最低(注射后5分钟时为0.10±0.02%ID/g)。用8-OH-DPAT阻断后，海马体摄取明显降低，而小脑摄取略有增加。这一结果表明(99m)Tc(CO)(3)-MPPDTF配合物与5-HT(¹A)受体具有特异性结合。
