Evaluation of (-)-[18 F]Flubatine-specific binding: Implications for reference region approaches.

ABSTRACT: We aimed to characterize changes in binding of (-)-[18 F]Flubatine to ?4 ?2 *-nicotinic acetylcholine receptors (?4 ?2 *-nAChRs) during a tobacco cigarette smoking challenge. Displacement of (-)-[18 F]Flubatine throughout the brain was quantified as change in (-)-[18 F]Flubatine distribution volume (VT ), with particular emphasis on regions with low VT . Three tobacco smokers were imaged with positron emission tomography (PET) during a 210 min bolus-plus-constant infusion of (-)-[18 F]Flubatine. A tobacco cigarette was smoked in the PET scanner ?125 min after the start of (-)-[18 F]Flubatine injection. Equilibrium analysis was used to estimate VT at baseline (90-120 min) and after cigarette challenge (180-210 min), at the time of greatest receptor occupancy by nicotine. Smoking reduced VT by 21?±?9% (average ±SD) in corpus callosum, 17?±?9% in frontal cortex, 36?±?11% in cerebellum, and 22?±?10% in putamen. The finding of displaceable (-)-[18 F]Flubatine binding throughout the brain is an important consideration for reference region-based quantification approaches with this tracer. We observed displacement of (-)-[18 F]Flubatine binding to ?4 ?2 *-nicotinic acetylcholine receptors in corpus callosum by a tobacco cigarette challenge. We conclude that reference region approaches utilizing corpus callosum should first perform careful characterization of displaceable (-)-[18 F]Flubatine binding and nondisplaceable kinetics in this putative reference region.

SUBMITTER: Bhatt S 

PROVIDER: S-EPMC6547815 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature