Besret L, Dauphin F, Huard C, Lasne M C, Vivet R, Mickala P, Barbelivien A, Baron J C
CEA/DSV/DRIPP, Centre Cyceron, Caen, France.
Nucl Med Biol. 1996 Feb;23(2):169-71. doi: 10.1016/0969-8051(95)02008-x.
In vivo pharmacokinetic and brain binding characteristics of [18F]RP 62203, a selective high-affinity serotonergic 5-HT2A receptor antagonist, were assessed in the rat following intravenous injection of trace amount of the radioligand. The radioactive distribution profile observed in the brain 60 min after injection was characterized by greater than fourfold higher uptake in neocortex as compared to cerebellum (0.38 +/- 0.07% injected dose/g, % ID/g and 0.08 +/- 0.01 ID/g, respectively), consistent with in vivo specific binding to the 5-HT2A receptor. Furthermore, specific [18F]RP 62203 binding significantly correlated with the reported in vitro distribution of 5-HT2A receptors, but not with known concentration profiles of dopaminergic D2 or adrenergic alpha 1 receptors. Finally, detectable specific binding was abolished by pretreatment with large doses of ritanserin, a selective 5-HT2A antagonist, which resulted in uniform uptakes across cortical, striatal and cerebellar tissues. Thus, [18F]RP 62203 appears to be a promising selective tool to visualize and quantify 5-HT2A brain receptors in vivo with positron emission tomography.
在静脉注射微量放射性配体[18F]RP 62203后，在大鼠体内评估了其药代动力学和脑结合特性。[18F]RP 62203是一种选择性高亲和力血清素能5-HT2A受体拮抗剂。注射后60分钟在脑中观察到的放射性分布特征为，新皮质的摄取量比小脑高四倍以上（分别为0.38±0.07%注射剂量/克，%ID/克和0.08±0.01 ID/克），这与体内与5-HT2A受体的特异性结合一致。此外，[18F]RP 62203的特异性结合与报道的5-HT2A受体体外分布显著相关，但与多巴胺能D2或肾上腺素能α1受体的已知浓度分布无关。最后，用大剂量的利坦色林（一种选择性5-HT2A拮抗剂）预处理可消除可检测到的特异性结合，从而使皮质、纹状体和小脑组织的摄取均匀。因此，[18F]RP 62203似乎是一种有前景的选择性工具，可用于正电子发射断层扫描在体内可视化和定量5-HT2A脑受体。
