摘要
The synthesis and biological evaluation of serotonin (5-HTB1AB) imaging agent [P131PI]- 4-iodo-N-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]-ethyl}-N-pridin-2-yl-benzamide ([P131PI]MPPI ) are reported. The chemical structure of aimed compound and intermediates were confirmed by IR, P1PHNMR, and MS. Radiochemical purity was above 99% determined by TLC. Biodistribution of [P131PI]MPPI in rats displayed high uptake in hippocam-pus and low uptake in cerebellum. The ratio of the uptake of [P131PI]MPPI in hippocampus to that in cerebellum was 2.90 at 30 min post injection. The radioactivity in thyroid was 0.069 and 0.128% ID/g organ at 5 min and 120 min, respectively, and it was increased with time, which suggests that in vivo deiodination may be the major route of me-tabolism. Ex vivo autoradiography of brain section displayed significant decrease of radioactivity in hippocampus when pretreated with 8-OH-DPAT, a selective 5HTB1AB agonist, compared with control. These findings strongly sug-gested that P131PI-MPPI could be used as an in vivo marker for studies of pharmacology of the 5-HTB1AB receptor system in animals.
The synthesis and biological evaluation of serotonin （5-HT1A） imaging agent [^131I]- 4-iodo-N-{2-[4-（2-methoxyphenyl）-piperazin-l-yl]-ethyl}-N-pridin-2-yl-benzamide （[^131I]MPPI） are reported. The chemical structure of aimed compound and intermediates were confirmed by IR, ^1HNMR, and MS. Radiochemical purity was above 99% determined by TLC. Biodistribution of [^131I]MPPI in rats displayed high uptake in hippocampus and low uptake in cerebellum. The ratio of the uptake of [^131I]MPPI in hippocampus to that in cerebellum was 2.90 at 30 rain post injection. The radioactivity in thyroid was 0.069 and 0.128% ID/g organ at 5 min and 120 rain, respectively, and it was increased with time, which suggests that in vivo deiodination may be the major route of metabolism. Ex vivo autoradiography of brain section displayed significant decrease of radioactivity in hippocampus when pretreated with 8-OH-DPAT, a selective 5HT1A agonist, compared with control. These findings strongly suggested that ^131I-MPPI could be used as an in vivo marker for studies of pharmacology of the 5-HT1A receptor system in animals.
基金
Supported by grants from National Natural Science Foundation of China (30470496)
"135" Medicinal Momentous Project of Jiangsu Province (RC2002068)
Jiangsu Natural Science Foundation (BK2004423)
Department of Personnel, Jiangsu Province (2003-07).
关键词
动物研究
放射性同位素元素示踪
成像
生物评估
5-HT1A, [^131I]MPPI, Synthesis, Biological evaluation, Imaging agent, Biodistribution
