Synthesis and Characterization of Binding of 5‐[76Br] Bromo‐3‐[[2(S)‐Azetidinyl]methoxy]pyridine, a Novel Nicotinic Acetylcholine Receptor Ligand, in Rat Brain

: 5‐[76Br]Bromo‐3‐[[2(S)‐azetidinyl]methoxy]‐pyridine ([76Br]BAP), a novel nicotinic acetylcholine receptor ligand, was synthesized using [76Br]bromide in an oxidative bromodestannylation of the corresponding trimethylstannyl compound. The radiochemical yield was 25%, and the specific radioactivity was on the order of 1 Ci/μmol. The binding properties of [76Br]BAP were characterized in vitro and in vivo in rat brain, and positron emission tomography (PET) experiments were performed in two rhesus monkeys. In association experiments on membranes of the cortex and thalamus, >90% of maximal specific [76Br]BAP binding was obtained after 60 min. The dissociation half‐life of [76Br]BAP was 51 ± 6 min in cortical membranes and 56 ± 3 min in thalamic membranes. Saturation experiments with [76Br]BAP revealed one population of binding sites with dissociation constant (KD) values of 36 ± 9 and 30 ± 9 pM in membranes of cortex and thalamus, respectively. The maximal binding site density (Bmax) values were 90 ± 17 and 207 ± 33 fmol/mg in membranes of cortex and thalamus, respectively. Scatchard plots were nonlinear, and the Hill coefficients were