Convenient Synthesis Of F-18-Radiolabeled R-(-)-N-N-Propyl-2-(3-Fluoropropanoxy-11-Hydroxynoraporphine

Aporphines are attractive candidates for imaging D-2 receptor function because, as agonists rather than antagonists, they are selective for the receptor in the high affinity state. In contrast, D-2 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 D-2 dysregulation, such as schizophrenia and Parkinson's disease. Accordingly, MCL-536 (R-(-)-N-n-propyl-2-(3-[F-18]fluoropropanoxy-11-hydroxynoraporphine) was selected for labeling with F-18 based on in vitro data obtained for the non-radioactive (F-19) compound. Fluorine-18-labeled MCL-536 was synthesized in 70% radiochemical yield, >99% radiochemical purity, and specific activity of 167GBq/mu mol (4.5Ci/mu mol) using p-toluenesulfonyl (tosyl) both as a novel protecting group for the phenol and a leaving group for the radiofluorination.