Elsinga Philip H, Hatano Kentaro, Ishiwata Kiichi
Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, The Netherlands.
Curr Med Chem. 2006;13(18):2139-53. doi: 10.2174/092986706777935258.
The dopaminergic system plays a major role in neurological and psychiatric disorders such as Parkinson's disease, Huntington's disease, tardive dyskinea and schizophrenia. Knowledge on altered dopamine synthesis, receptor densities and status are important for understanding the mechanisms underlying the pathogenesis and therapy of diseases. PET provides a non-invasive tool to investigate these features in vivo, provided the availability of suitable radiopharmaceuticals. To investigate presynaptic function, PET-tracers have been developed to measure dopamine synthesis and transport. For the former the most commonly used tracers are 6-[(18)F]FDOPA and 6-[(18)F]FMT, whereas for the latter several (11)C/(18)F-labeled tropane analogues are being clinically used. Postsynaptically, dopamine exerts actions through several subtypes of the dopamine receptor. The dopamine receptor family consists of 5 subtypes D(1)-D(5). In order to investigate the role of each receptor subtype, selective and high-affinity PET-radioligands are required. For the dopamine D(1)-subtype the most commonly used ligand is [(11)C]SCH 23390 or [(11)C]NNC 112, whereas for the D(2)/D(3)-subtype [(11)C]raclopride is a common tracer. [(18)F]Fallypride is a suitable PET-tracer for the investigation of extrapyramidal D(2)-receptors. For the other subtypes no suitable radioligands have been developed yet. This paper gives an overview of the current status on dopamine PET-tracers and the development of new lead compounds as potential PET-tracers by medicinal chemistry.
多巴胺能系统在帕金森病、亨廷顿病、迟发性运动障碍和精神分裂症等神经和精神疾病中起主要作用。了解多巴胺合成、受体密度和状态的改变对于理解疾病发病机制和治疗的潜在机制很重要。正电子发射断层扫描（PET）提供了一种在体研究这些特征的非侵入性工具，前提是有合适的放射性药物。为了研究突触前功能，已开发出PET示踪剂来测量多巴胺的合成和转运。对于前者，最常用的示踪剂是6-[(18)F]氟多巴（6-[(18)F]FDOPA）和6-[(18)F]氟甲基酪氨酸（6-[(18)F]FMT），而对于后者，几种(11)C/(18)F标记的托烷类似物正在临床使用。在突触后，多巴胺通过多巴胺受体的几种亚型发挥作用。多巴胺受体家族由5种亚型D(1)-D(5)组成。为了研究每种受体亚型的作用，需要选择性和高亲和力的PET放射性配体。对于多巴胺D(1)亚型，最常用的配体是[(11)C]SCH 23390或[(11)C]NNC 112，而对于D(2)/D(3)亚型，[(11)C]雷氯必利是一种常用的示踪剂。[(18)F]氟哌利多是用于研究锥体外系D(2)受体的合适PET示踪剂。对于其他亚型，尚未开发出合适的放射性配体。本文概述了多巴胺PET示踪剂的现状以及通过药物化学开发作为潜在PET示踪剂的新先导化合物的情况。
