Work

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

Year: 2017

Type: article

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 lowVT. 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 estimateVTat baseline (90‐120 min) and after cigarette challenge (180‐210 min), at the time of greatest receptor occupancy by nicotine. Smoking reducedVTby 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 nondisplaceable kinetics in this putative reference region.

Source: Synapse

DOI: 10.1002/syn.22016