2-[18F]Fluoro-A-85380:: A novel pet ligand for nicotinic acetylcholine receptors

The density of brain nicotinic acetylcholine receptors (nAChRs) in Rhesus monkey was measured in vivo by PET with 2-[F-18]fluoro-3-(2(S)-azetidinylmethoxy (2-[F-18]Fluoro-A-85380). The results of blocking studies with cytisine suggested the use of cerebellum for estimation of non-specific ligand accumulation in the thalamus. Therefore, the specific binding (SB) was measured as a difference between the total radioactivity in the thalamus and that in the cerebellum. The saturation of 2-fluoro-A-85380 SE in the thalamus was analyzed on the same animal by administering different masses of the ligand. Our results demonstrated that the SE in the thalamus was saturable. The ligand at a dose of 70 nmol/kg occupied 85% of nAChRs and at a dose of ca. 8.7 nmol/kg (ED50) 50% of nAChRs Using Scatchard analysis, the density of nAChRs in Rhesus monkey thalamus in vivo was calculated as ca. 5.5 pmol/g tissue. This value was in close agreement with estimates from in vitro assays of Rhesus monkey brain tissue.