18F 标记的 R-(-)-N-正丙基-2-(3-氟丙氧基)-11-羟基去甲阿朴啡的简便合成
Convenient synthesis of 18F-radiolabeled R-(-)-N-n-propyl-2-(3-fluoropropanoxy-11-hydroxynoraporphine.
作者信息
Sromek Anna W, Zhang Shaohui, Akurathi Vamsidhar, Packard Alan B, Li Wei, Alagille David, Morley Thomas J, Baldwin Ronald, Tamagnan Gilles, Neumeyer John L
机构信息
Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA, 02478-9106, USA.
出版信息
J Labelled Comp Radiopharm. 2014 Dec;57(14):725-9. doi: 10.1002/jlcr.3246. Epub 2014 Nov 17.
Aporphines are attractive candidates for imaging D2 receptor function because, as agonists rather than antagonists, they are selective for the receptor in the high affinity state. In contrast, D2 antagonists do not distinguish between the high and low affinity states, and in vitro data suggests that this distinction may be important in studying diseases characterized by D2 dysregulation, such as schizophrenia and Parkinson's disease. Accordingly, MCL-536 (R-(-)-N-n-propyl-2-(3-[(18)F]fluoropropanoxy-11-hydroxynoraporphine) was selected for labeling with (18)F based on in vitro data obtained for the non-radioactive ((19)F) compound. Fluorine-18-labeled MCL-536 was synthesized in 70% radiochemical yield, >99% radiochemical purity, and specific activity of 167 GBq/µmol (4.5 Ci/µmol) using p-toluenesulfonyl (tosyl) both as a novel protecting group for the phenol and a leaving group for the radiofluorination.
阿朴啡因是用于成像D2受体功能的有吸引力的候选物，因为作为激动剂而非拮抗剂，它们对高亲和力状态的受体具有选择性。相比之下，D2拮抗剂无法区分高亲和力状态和低亲和力状态，体外数据表明这种区分在研究以D2失调为特征的疾病（如精神分裂症和帕金森病）中可能很重要。因此，基于非放射性（19F）化合物的体外数据，选择MCL-536（R-（-）-N-正丙基-2-（3-[(18)F]氟丙氧基-11-羟基去甲阿朴啡）用（18）F进行标记。使用对甲苯磺酰基（tosyl）作为酚的新型保护基团和放射性氟化的离去基团，以70%的放射化学产率、>99%的放射化学纯度和167 GBq/µmol（4.5 Ci/µmol）的比活度合成了氟-18标记的MCL-536。
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