[18F]AZAN

(18)F-AZAN was synthesized using a modified (18)F-FDG synthesis module. The regional distribution of (18)F-AZAN in the brain was evaluated in baseline and cytisine-blocking studies of 4 male Papio anubis baboons. PET modeling procedures were used for calculation of regional distribution volume (V(T)), nondisplaceable binding potential (BP(ND)), and receptor occupancy.

(18)F-AZAN rapidly entered the baboon brain, reached a steady state within 90 min after injection, and specifically labeled cerebral nAChRs. The peak radioactivity in the thalamus was 540 (percentage standardized uptake value) at 18 ± 7 min (n = 4) after bolus injection. Mathematical data analysis demonstrated that scanning for only 90 min is sufficient for determination of PET outcome variables (BP(ND), 3.2 [unitless] and V(T), 32-35 mL/mL in thalamus). The dose-dependent blocking experiments with cytisine demonstrated that (18)F-AZAN binds specifically with β2-containing (predominantly α4β2) nAChRs.

(18)F-AZAN specifically labels nAChRs in baboon brains with a high value of BP(ND) and it requires only 90 min of PET scanning to produce estimates of V(T) and BP(ND) in the various brain regions. The blocking of nAChRs with cytisine is dose-dependent and it showed that (18)F-AZAN is suitable for application in nicotinic drug evaluation. In summary, (18)F-AZAN is superior to 2-(18)F-FA and 6-(18)F-FA for imaging cerebral β2-containing nAChRs in baboons. Further evaluations of (18)F-AZAN in the human brain are under way.