Halldin C, Farde L, Högberg T, Mohell N, Hall H, Suhara T, Karlsson P, Nakashima Y, Swahn C G
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
J Nucl Med. 1995 Jul;36(7):1275-81.
D2 dopamine receptors in extrastriatal brain regions are of central interest for research in schizophrenia and antipsychotic drugs. This article reports the development of [11C]FLB 457 for PET examination of extrastriatal D2 dopamine receptors.
Carbon-11-FLB 457 was prepared by O-methylation of FLB 604 (2-hydroxy precursor) with [11C]methyl iodide. Total radiochemical yield was 25%-35% within a total synthesis time of 30 min. The specific radioactivity at the end of synthesis was about 1300 Ci/mmole (48 GBq/mumole).
FLB 457 bound with high affinity to D2 and D3 dopamine receptors, whereas binding to other putative central receptors was negligible. PET studies in Cynomolgus monkeys demonstrated 15 times higher accumulation of radioactivity in the striatum than in the cerebellum after 60 min. Uptake in the thalamus and neocortex, extrastriatal regions with a low density of D2 dopamine receptors, was, respectively, 4 and 2.5 times higher than in the cerebellum. Radioactivity was displaced by raclopride and haloperidol which confirms the selectivity and reversibility of [11C]FLB 457 binding to D2 dopamine receptors in vivo in the striatum, thalamus and neocortex.
Carbon-11-FLB 457 should be a useful PET ligand for quantitative examination of D2 dopamine receptors in extrastriatal regions in the human brain.
脑纹状体以外区域的D2多巴胺受体是精神分裂症和抗精神病药物研究的核心关注点。本文报道了用于脑纹状体以外区域D2多巴胺受体PET检查的[11C]FLB 457的研发情况。
通过用[11C]甲基碘对FLB 604（2-羟基前体）进行O-甲基化制备碳-11-FLB 457。在30分钟的总合成时间内，总放射化学产率为25%-35%。合成结束时的比活度约为1300居里/毫摩尔（48吉贝可/微摩尔）。
FLB 457与D2和D3多巴胺受体具有高亲和力结合，而与其他假定的中枢受体的结合可忽略不计。食蟹猴的PET研究表明，60分钟后纹状体中的放射性积累比小脑中高15倍。丘脑和新皮层（D2多巴胺受体密度低的脑纹状体以外区域）的摄取分别比小脑中高4倍和2.5倍。放射性被雷氯必利和氟哌啶醇取代，这证实了[11C]FLB 457在纹状体、丘脑和新皮层中体内与D2多巴胺受体结合的选择性和可逆性。
碳-11-FLB 457应该是用于定量检测人脑脑纹状体以外区域D2多巴胺受体的有用PET配体。
