Greater Nicotinic Acetylcholine Receptor Density in Smokers Than in Nonsmokers: A PET Study with 2-18F-FA-85380

Assays of human postmortem brain tissue have revealed that smokers have greater densities of high-affinity nicotinic acetyl-choline receptors (nAChRs) in several brain regions than do non-smokers or exsmokers. Quantitative PET imaging of nAChRs in humans has recently been reported using the a4b2 * subtype– specific radioligand 2-18F-FA-85380 (2FA). Methods: We used PET and 2FA to measure total volumes of distribution corrected for the free fraction of 2FA in plasma (VT/fP) in 10 nonsmokers and 6 heavy smokers (.14 cigarettes/d; abstinent for.36 h). Dy-namic PET scans were performed over 8 h, commencing imme-diately after a bolus injection of 2FA. Anatomic sampling was performed on PET images that were coregistered to MR images acquired from each volunteer. Data were analyzed by Logan plots and by 1- and 2-tissue-compartment models using un-bound, unmetabolized arterial 2FA concentration as the inpu