Preparation And Biodistribution Of Tc-99-Tricarbonyl Complex With 4-[(2-Methoxyphenyl)Piperazin-1-Yl]-Dithioformate As A Potential 5-Ht1a Receptor Imaging Agent

The goal of this study is to develop a novel 5-HT1A receptor imaging agent. 4-[(2-methoxyphenyl)piperazin-l-yl]-dithioformate (MPPDTF) was labeled with Te-99m-tricarbonyl core via dithioformate moiety in high yield (> 96% by HPLC). Tc-99m(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 120min) and good retention (about 80% of the activity was retained in the brain at 120min post-injection). Regional brain distribution study showed that hippocampus, where the 5-HT1A receptor density is high, had the highest uptake (0.60 +/- 0.02% ID/g at 5min p.i.) and the cerebellum, where the 5-HT1A receptor density is low, had the lowest uptake (0.10 +/- 0.02% ID/g at 5min 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 Tc-99m(CO)(3)-MPPDTF complex has specific binding to 5-HT1A receptor. (c) 2006 Elsevier Ltd. All rights reserved.