Preparation and biodistribution of 99mTc-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-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.
Zhang
Xianzhong
X
College of Chemistry, Beijing Normal University, Beijing, 100875, PR China. zhangxzh@gmail.com <zhangxzh@gmail.com>
Zhou
Panwang
P
Liu
Jiaojiao
J
Huang
Yan
Y
Lin
Yan
Y
Chen
Yanling
Y
Gu
Ting
T
Yang
Wenjiang
W
Wang
Xuebin
X
D000818:Animals; D001921:Brain / Q000378:metabolism; D005561:Formates / Q000138:chemical synthesis / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods*; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D044282:Receptor, Serotonin, 5-HT1A / Q000032:analysis*; D013667:Technetium; D014018:Tissue Distribution
D005561:Formates; D010879:Piperazines; D019275:Radiopharmaceuticals; C518393:technetium 99m tricarbonyl 4-((2-methoxyphenyl)piperazin-1-yl)dithioformate; D044282:Receptor, Serotonin, 5-HT1A; D013667:Technetium