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

Abstract We aimed to characterize changes in binding of (‐)‐[18F]Flubatine to α4β2*‐nicotinic acetylcholine receptors (α4β2*‐nAChRs) during a tobacco cigarette smoking challenge. Displacement of (‐)‐[18F]Flubatine throughout the brain was quantified as change in (‐)‐[18F]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 (‐)‐[18F]Flubatine. A tobacco cigarette was smoked in the PET scanner ∼125 min after the start of (‐)‐[18F]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 (‐)‐[18F]Flubatine binding throughout the brain is an important consideration for reference region‐based quantification approaches with this tracer. We observed displacement of (‐)‐[18F]Flubatine binding to α4β2*‐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 (‐)‐[18F]Flubatine binding and nondisplace...
Source: Synapse - Category: Neurology Authors: Tags: RESEARCH ARTICLE Source Type: research