Pike V W, McCarron J A, Lammertsma A A, Osman S, Hume S P, Sargent P A, Bench C J, Cliffe I A, Fletcher A, Grasby P M
MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Eur J Pharmacol. 1996 Apr 22;301(1-3):R5-7. doi: 10.1016/0014-2999(96)00079-9.
The 5-HT1A receptor antagonist, WAY-100635 [N-(2-(4-(2-methoxyphenyl)- 1-piperazinyl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide], was labelled in its carbonyl group with carbon-11 (t1/2 = 20.4 min), injected intravenously into healthy male volunteers and studied with positron emission tomography (PET). The acquired data provide exquisite delineation of 5-HT1A receptors in brain, with the ratio of radioactivity uptake in receptor-rich regions, such as medial temporal cortex, to that in receptor-devoid cerebellum reaching 25 by 60 min after radioligand injection. Application of biomathematical modelling to the data revealed high values (7.8) for binding potential, a measure of Bmax/Kp, in receptor-rich regions. Only very polar radioactive metabolites were present in plasma, a finding consistent with the low level of nonspecific binding seen in cerebellum. [carbonyl-11C]WAY-100635 is concluded to be far superior to the previously reported [0-methyl-11C]WAY-100635 as a radioligand for PET studies of 5-HT1A receptors in human brain.
5-羟色胺1A受体拮抗剂WAY-100635 [N-(2-(4-(2-甲氧基苯基)-1-哌嗪基)乙基)-N-(2-吡啶基)环己烷甲酰胺] 的羰基用碳-11（半衰期 = 20.4分钟）进行标记，静脉注射到健康男性志愿者体内，并采用正电子发射断层扫描（PET）进行研究。所获取的数据精确描绘了大脑中的5-羟色胺1A受体，放射性配体注射后60分钟时，富含受体的区域（如颞叶内侧皮质）与缺乏受体的小脑的放射性摄取比值达到25。对数据应用生物数学建模显示，富含受体区域的结合潜能（衡量Bmax/Kp的指标）值较高（7.8）。血浆中仅存在极性很强的放射性代谢物，这一发现与小脑中观察到的低非特异性结合水平一致。结论是，[羰基-11C]WAY-100635作为用于人脑5-羟色胺1A受体PET研究的放射性配体，远比先前报道的[0-甲基-11C]WAY-100635优越。
