Characterization of the nicotinic ligand 2-[F-18]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine in vivo

The biodistribution of the nicotinic acetylcholine receptor (nAChR) radioli gand 2[F-18]fluoro-3-2(S)-2-azetidinylmethoxylpyridine ([F-18]fluoro-A-8538 0, half-life of fluorine-18 = 110 min) in selected rat brain areas was asse ssed in vivo. The radiotracer showed a good penetration in the brain. The r egional distribution of the radioligand was consistent with the density of nAChRs determined from previous studies in vitro. Sixty minutes post-inject ion, the highest uptake was observed in the thalamus, (1% I.D. /g tissue), an intermediate one in the frontal cortex (0.78% I.D. /g tissue), and the l owest in the cerebellum (0.5% I.D. /g tissue). Pretreatment with several nA ChR ligands (nicotine, cytisine, epibatidine, unlabeled fluoro-A85380) subs tantially reduced uptake of the radioligand in the three cerebral areas. Pr etreatment with the nAChR channel blocker mecamylamine or with the muscarin ic receptor antagonist dexetimide had no appreciable effect on the uptake o f fluoro-A-85380. These results support the high in vivo selectivity and sp ecificity of fluoro-A-85380. Therefore, [F-18]fluoro-A-85380 may be useful for positron emission tomography study of nAChRs in humans. (C) 1998 Elsevi er Science Inc.