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Basic Science Investigation |
1 Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland; 2 Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; and 3 Preclinical Pharmacology Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland
Correspondence: For correspondence or reprints contact: Alexey G. Mukhin, MD, PhD, Center for Nicotine and Smoking Cessation Research, Department of Psychiatry, Duke University Medical Center, 24224 Erwin Rd., Suite 201, Durham, NC 27705. E-mail: a.mukhin{at}duke.edu
The aim of the present study was to explore the applicability of an extracerebral reference region for the quantification of cerebral receptors with PET. Methods: Male squirrel monkeys underwent quantitative PET studies of cerebral nicotinic acetylcholine receptors (nAChRs) with 2-18F-fluoro-A-85380 (2-FA). Data from dynamic PET scans were analyzed with various compartment- and non–compartment-based models, including a simplified reference tissue model (SRTM). Nondisplaceable volume-of-distribution (VDnd) values were determined in regions of interest after the blockade of 2-FA–specific binding by nicotine infusion. Binding potential values, estimated with the cerebellum and muscle as reference regions, were compared and the reproducibility of measurements was determined. Results: One- and 2-tissue-compartment modeling and linear graphic analysis provided similar total volume-of-distribution (VDT) values for each studied region. VDT values were high in the thalamus, intermediate in the cortex and midbrain, and low in the cerebellum and muscle, consistent with the distribution pattern of nAChR containing 
4 and ß2 receptor subunits (4ß2*). The administration of nicotine at 2 mg/kg/d via an osmotic pump resulted in a nearly complete saturation of 2-FA–specific binding and led to very small changes in volumes of distribution in the cerebellum and muscle (–9% ± 4% [mean ± SEM] and 0% ± 6%, respectively), suggesting limited specific binding of the radioligand in these areas. VDT measured in muscle in 15 monkeys was reasonably constant (3.0 ± 0.2, with a coefficient of variation of 8%). VDnd in studied brain regions exceeded VDT in muscles by a factor of 1.3. With this factor and with muscle as a reference region, BP* values calculated for studied brain regions with the SRTM were in good agreement with those obtained with the cerebellum as a reference region. Significant correlations were observed between BP* values estimated with these 2 approaches. The reproducibilities of BP* measurements obtained with the 2 methods were comparable, with coefficients of variation of less than 11% and 13% for the thalamus and the cortex, respectively. Conclusion: These results suggest that the accurate quantification of nAChRs can be performed with 2-FA and a reference region outside the brain, providing a novel approach for the quantification of brain receptors when no suitable cerebral reference region is available.
Key Words: PET • nonhuman primates • radioligand • in vivo binding • nicotinic acetylcholine receptors
COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.
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