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Evaluation of (‐)‐[ 18 F]F lubatine‐specific binding: Implications for reference region approaches
Author(s) -
Bhatt Shivani,
Hillmer Ansel T.,
Nabulsi Nabeel,
Matuskey David,
Lim Keunpoong,
Lin ShuFei,
Esterlis Irina,
Carson Richard E.,
Huang Yiyun,
Cosgrove Kelly P.
Publication year - 2018
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.22016
Subject(s) - binding potential , corpus callosum , nicotine , nuclear medicine , acetylcholine receptor , nicotinic agonist , positron emission tomography , putamen , chemistry , nicotinic acetylcholine receptor , receptor , neuroscience , nuclear magnetic resonance , medicine , psychology , biochemistry , physics
We aimed to characterize changes in binding of (‐)‐[ 18 F]Flubatine to α 4 β 2 *‐nicotinic acetylcholine receptors (α 4 β 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 ( V T ), with particular emphasis on regions with low V T . 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 V T at baseline (90‐120 min) and after cigarette challenge (180‐210 min), at the time of greatest receptor occupancy by nicotine. Smoking reduced V T 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 α 4 β 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.