Preparation of 11C-labelled SCH 23390 for the in vivo study of dopamine D-1 receptors using positron emission tomography.

The dopamine D-1 receptor antagonist, SCH 23390 ((R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepin-7-ol), was labelled by alkylation of the desmethyl compound SCH 24518 ((R)-(+)-8-chloro-2,3,4,5-tetrahydro-5-phenyl-1H-3-benzazepin-7- ol) with [11C]methyl iodide. A multivariate optimization method, Simplex, was employed to obtain the optimal radiochemical yield. Both straight-phase and reversed-phase preparative HPLC were investigated in the purification of [11C]SCH 23390. Reaction in acetone with subsequent straight-phase LC separation resulted in 80% radiochemical yield, based on [11C]methyl iodide, with a total synthesis time of 35-40 min and a radiochemical purity greater than 99%. The average specific activity was on the order of 11.1 GBq/mmol. The 11C-labelled SCH 23390 was used to visualize the dopamine D-1 receptor-rich areas of a monkey brain by positron emission tomography. The data obtained showed a rapid distribution of radioactivity into the brain and a conspicuous accumulation of [11C]SCH 23390 in the striatum.