(3-N-[¹¹C]methyl)spiperone, a ligand binding to dopamine receptors: Radiochemical synthesis and biodistribution studies in mice

Carbon-11-labeled 3-N-methylspiperone, a positron-emitting dopamine-receptor antagonist with potential for use in positron emission tomography studies of human neurotransmitter receptors, was synthesized from ¹¹CO₂ in 40 min, with a radiochemical yield of ~20-40%. The specific activity of the (3-N-[¹¹C]methyl)-spiperone was determined by ultraviolet spectroscopy to be approximately 270 mCi/μmol at the end of synthesis. In in vitro binding experiments, the K(i) for 3-N-methylspiperone was found to be approximately 250 pM (against H-3 spiperone). The brain-to-blood ratios in normal ICR mice were 2.8 or greater at the times studied, and the striatum-to-cerebellum ratio at 60 min after injection was 20:1.