RT Journal Article SR Electronic T1 PET Imaging of High-Affinity α4β2 Nicotinic Acetylcholine Receptors in Humans with 18F-AZAN, a Radioligand with Optimal Brain Kinetics JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1308 OP 1314 DO 10.2967/jnumed.112.108001 VO 54 IS 8 A1 Dean F. Wong A1 Hiroto Kuwabara A1 Jongho Kim A1 James R. Brašić A1 Wichana Chamroonrat A1 Yongjun Gao A1 Heather Valentine A1 William Willis A1 Anil Mathur A1 Mary E. McCaul A1 Gary Wand A1 Emily G. Gean A1 Robert F. Dannals A1 Andrew G. Horti YR 2013 UL http://jnm.snmjournals.org/content/54/8/1308.abstract AB We evaluated (−)-2-(6-[18F]fluoro-2,3′-bipyridin-5′-yl)-7-methyl-7-aza-bicyclo[2.2.1]heptane (18F-AZAN), a novel radiotracer that binds to α4β2 nicotinic acetylcholine receptors (α4β2-nAChRs) and shows high specific binding and rapid and reversible kinetics in the baboon and human brain. Methods: We tested safety tolerability and test–retest reliability (n = 5) and proposed initial quantification of 18F-AZAN receptors in 3 healthy human subjects who had nicotine exposure and 9 who did not. We also present a receptor blocking study in a nicotine subject dosed with the α4β2-nAChR–selective partial agonist varenicline. Results: Radiation dosimetry PET/CT experiments indicated that most human organs received doses between 0.008 and 0.015 mSv/MBq, with an effective dose of approximately 0.014 mSv/MBq. The tracer rapidly entered the brain, and the peak was reached before 20 min, even for thalamus. Ninety-minute scans were sufficient for 18F-AZAN to obtain the ratio at equilibrium of specifically bound radioligand to nondisplaceable radioligand in tissue (BPND) using plasma reference graphical analysis, which showed excellent reproducibility of BPND (test–retest variability < 10%) in the nAChR-rich brain regions. Regional plasma reference graphical analysis BPND values exceeded 2 in the midbrain tegmental nuclei, lateral geniculate body, and thalamus for nonsmokers (n = 9) but were less than 1 in the nAChR-poor brain regions. There was a dramatic reduction of 18F-AZAN brain uptake in smokers and varenicline-treated subjects. Conclusion: 18F-AZAN is a highly specific, safe, and effective PET radioligand for human subjects that requires only 90 min of PET scanning to estimate high-affinity α4β2-nAChR in the living human brain.