RT Journal Article SR Electronic T1 Greater Nicotinic Acetylcholine Receptor Density in Smokers Than in Nonsmokers: A PET Study with 2-18F-FA-85380 JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1628 OP 1635 DO 10.2967/jnumed.108.050716 VO 49 IS 10 A1 Alexey G. Mukhin A1 Alane S. Kimes A1 Svetlana I. Chefer A1 John A. Matochik A1 Carlo S. Contoreggi A1 Andrew G. Horti A1 D. Bruce Vaupel A1 Olga Pavlova A1 Elliot A. Stein YR 2008 UL http://jnm.snmjournals.org/content/49/10/1628.abstract AB Assays of human postmortem brain tissue have revealed that smokers have greater densities of high-affinity nicotinic acetylcholine receptors (nAChRs) in several brain regions than do nonsmokers or exsmokers. Quantitative PET imaging of nAChRs in humans has recently been reported using the α4β2* 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). Dynamic PET scans were performed over 8 h, commencing immediately 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 unbound, unmetabolized arterial 2FA concentration as the input function. Results: All modeling methods yielded similar results. VT/fP was significantly higher in smokers than in nonsmokers in all brain regions tested, except the thalamus. We used measures of VT/fP and estimates of nondisplaceable volume of distribution and found 25%–200% higher values in smokers than in nonsmokers for the volume of distribution for the specific binding compartment in the frontal cortex, midbrain, putamen, pons, cerebellum, and corpus callosum. These findings were consistent with voxel-based analysis using statistical parametric mapping. Conclusion: Our findings suggest that PET with 2FA can be used to study the role of nicotine-induced upregulation of nAChRs in active smokers and during smoking cessation.