Lundkvist C, Halldin C, Ginovart N, Nyberg S, Swahn C G, Carr A A, Brunner F, Farde L
Karolinska Institutet, Department of Clinical Neuroscience] Stockholm, Sweden.
Life Sci. 1996;58(10):PL 187-92. doi: 10.1016/0024-3205(96)00013-6.
The highly selective 5-HT2A receptor antagonist, MDL 100907 ((R)-(+)-4 -(l-hydroxy-1-(2,3-dimethoxyphenyl)methyl)-N -2-(4-fluorophenylethyl)piperidine), was labeled with 11C for Positron Emission Tomography (PET) studies. After i.v. injection of (R)-(+)-[3-OCH3-11C]MDL 100907 [11C]MDL 100907) in Cynomolgus monkeys a marked accumulation in the 5-HT2A receptor rich neocortical regions was obtained with a neocortex to cerebellum ratio of 3.5-4.5 after 60-80 minutes. In the neocortical regions a transient equilibrium occurred within 40-60 minutes. Radioactivity in the neocortex, but not in the cerebellum, was reduced after injection of ketanserin, indicating that neocortical radioactivity following injection of [11C]MDL 100907 represents specific binding to 5-HT2A receptors. There was no evident effect on neocortical binding after pretreatment with raclopride or SCH 23390. [11C]MDL 100907 has potential to become the first selective radioligand for PET-quantitation of 5-HT2A receptors in the human brain in vivo.
高选择性5-HT2A受体拮抗剂MDL 100907（(R)-(+)-4-(1-羟基-1-(2,3-二甲氧基苯基)甲基)-N-2-(4-氟苯乙基)哌啶）用11C进行标记，用于正电子发射断层扫描（PET）研究。在食蟹猴静脉注射(R)-(+)-[3-OCH3-11C]MDL 100907（[11C]MDL 100907）后，60至80分钟时在富含5-HT2A受体的新皮质区域有明显积聚，新皮质与小脑的比值为3.5至4.5。在新皮质区域，40至60分钟内出现短暂平衡。注射酮色林后，新皮质而非小脑的放射性降低，这表明注射[11C]MDL 100907后新皮质的放射性代表与5-HT2A受体的特异性结合。用雷氯必利或SCH 23390预处理后，对新皮质结合没有明显影响。[11C]MDL 100907有潜力成为用于在体定量人脑5-HT2A受体的首个PET选择性放射性配体。
