PET IMAGING STUDIES OF DOPAMINE D-2 RECEPTORS - COMPARISON OF [F-18] N-METHYLSPIPERONE AND THE BENZAMIDE ANALOGS [F-18]MABN AND [F-18] MBP IN BABOON BRAIN

A series of positron emission tomography (PET) imaging studies was con ducted in a baboon with the benzamide derivatives imethoxy-N-[9-(4-flu orobenzyl)-9-azabicyclo[3.3.1] nonan-3 beta-yl]benzamide ([F-18]MABN) and 2,3-dimethoxy-N-[1-(4-fluorobenzyl)piperidin-4-yl] benzamide ([F-1 8]MBP). Studies were also conducted with the butyrophenone [F-18]N-met hylspiperone (NMSP) for comparison. Tissue-time activity curves of [F- 18]MABN are similar to those of[F-18]NMSP since both compounds display ed approximately the same uptake in the basal ganglia and displayed ir reversible binding kinetics in vivo. However, the rapid rate of cleara nce from the cerebellum and high basal ganglia:cerebellum ratio of [F- 18]MABN indicate that this compound has a much lower amount of nonspec ific binding than [F-18]NMSP. [F-18]MBP displayed a higher uptake in t he basal ganglia relative to [F-18]NMSP and [F-18]MABN and exhibited r eversible binding kinetics in vivo. This property of [F-18]MBP is desi rable since the uptake of radioactivity in D-2-rich ligands is less li kely to be influenced by changes in cerebral blood flow. The current d ata suggest that both [F-18]MABN and [F-18]MBP are promising ligands f or studying dopamine D-2 receptors with PET. (C) 1995 Wiley-Liss, Inc.