TY - JOUR T1 - PET Imaging of High-Affinity α4β2 Nicotinic Acetylcholine Receptors in Humans with <sup>18</sup>F-AZAN, a Radioligand with Optimal Brain Kinetics JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1308 LP - 1314 DO - 10.2967/jnumed.112.108001 VL - 54 IS - 8 AU - Dean F. Wong AU - Hiroto Kuwabara AU - Jongho Kim AU - James R. Brašić AU - Wichana Chamroonrat AU - Yongjun Gao AU - Heather Valentine AU - William Willis AU - Anil Mathur AU - Mary E. McCaul AU - Gary Wand AU - Emily G. Gean AU - Robert F. Dannals AU - Andrew G. Horti Y1 - 2013/08/01 UR - http://jnm.snmjournals.org/content/54/8/1308.abstract N2 - 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 &lt; 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. ER -