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Synapse. 2018 Mar;72(3). doi: 10.1002/syn.22016. Epub 2017 Nov 17.

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

Author information

1
Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, Connecticut.
2
Yale PET Center, Yale University School of Medicine, New Haven, Connecticut.
3
Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut.
4
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
5
West Haven VA Hospital, National Center for PTSD, West Haven, Connecticut.

Abstract

We aimed to characterize changes in binding of (-)-[18 F]Flubatine to α4 β2 *-nicotinic acetylcholine receptors (α4 β2 *-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 α4 β2 *-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.

KEYWORDS:

positron emission tomography; reference region; tobacco smoking; white matter; α4β2*-nicotinic acetylcholine receptors

PMID:
29105121
DOI:
10.1002/syn.22016
[Indexed for MEDLINE]

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