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

The biodistribution of the nicotinic acetylcholine receptor (nAChR) radioligand 2-[18F]fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine ([18F]fluoro-A-85380, half-life of fluorine-18 = 110 min) in selected rat brain areas was assessed in vivo. The radiotracer showed a good penetration in the brain. The regional distribution of the radioligand was consistent with the density of nAChRs determined from previous studies in vitro. Sixty minutes post-injection, 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 lowest in the cerebellum (0.5% I.D./g tissue). Pretreatment with several nAChR ligands (nicotine, cytisine, epibatidine, unlabeled fluoro-A-85380) substantially reduced uptake of the radioligand in the three cerebral areas. Pretreatment with the nAChR channel blocker mecamylamine or with the muscarinic receptor antagonist dexetimide had no appreciable effect on the uptake of fluoro-A-85380. These results support the high in vivo selectivity and specificity of fluoro-A-85380. Therefore, [18F]fluoro-A-85380 may be useful for positron emission tomography study of nAChRs in humans.