11C-labeled cholecystokinin (CCK) receptor antagonists, 3R(+)-N-(2,3-dihydro-1-[11C]methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine- 3-yl)-N'-(3-methylphenyl)urea ([11C]L-365,260) and its (S)-enantiomer ([11C]L-365,346), have been synthesized and evaluated in vivo for use in CCK receptor studies with positron emission tomography (PET). Selective N-methylation of a racemic precursor with [11C]iodomethane and subsequent optical resolution of the racemate with HPLC afforded optically pure [11C]L-365,260 and [11C]L-365,346, which are selective for CCK-B (central-type) receptors and CCK-A (peripheral-type) receptors, respectively. Biodistribution studies in mice showed very low brain uptakes (<0.8% dose/gram) of the radioactivities after intravenous injections of these compounds, although that of brain CCK-B receptor-selective [11C]L-365,260 was 2-fold that of [11C]L-365,346. In peripheral organs, uptake of the radioactivity in the pancreas was the highest among the organs tested after the injection of [11C]L-365,346 and was 3-fold that of [11C]L-365,260. It was also observed that high uptake of [11C]L-365,346 in rat pancreas was significantly inhibited by a simultaneous injection with a large dose of L-365,346 (3 mg/kg). These preliminary results suggest that the nonpeptide CCK antagonist [11C]L-365,346 may be useful for probing pancreatic CCK-A receptors by PET. Owing to the very low brain permeability, however, [11C]L-365,260 may have no potential as a PET tracer for probing brain CCK-B receptors.