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

¹ Neuroimaging Research Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland; ² Office of the Clinical Director, National Institute on Drug Abuse Intramural Research Program, Department of Health and Human Services, National Institutes of Health, Baltimore, Maryland; and ³ Department of Radiology, Johns Hopkins University, Baltimore, Maryland

Correspondence: For correspondence or reprints contact: Alane S. Kimes, Neuroimaging Research Branch, National Institute on Drug Abuse Intramural Research Program, Department of Health and Human Services, National Institutes of Health, 251 Bayview Blvd., Baltimore, MD 21224. E-mail: akimes{at}intra.nida.nih.gov

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 4β2* 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 (V_T/f_P) 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. V_T/f_P was significantly higher in smokers than in nonsmokers in all brain regions tested, except the thalamus. We used measures of V_T/f_P 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.

Key Words: molecular imaging • PET • radiotracer tissue kinetics • neuroimaging • nicotinic acetylcholine receptors • smoking

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JNM 2008 49: 11A-12A. [Full Text]