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

Overview

Journal J Nucl Med

Specialty Nuclear Medicine

Date 2008 Sep 17

PMID 18794265

Citations 69

Authors

Alexey G Mukhin

Alane S Kimes

Svetlana I Chefer

John A Matochik

Carlo S Contoreggi

Andrew G Horti

D Bruce Vaupel

Olga Pavlova

Elliot A Stein

Affiliations

Soon will be listed here.

Abstract

Unlabelled: 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 alpha4beta2* subtype-specific radioligand 2-(18)F-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.

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