title: Imaging the cannabinoid CB1 receptor in humans with [11C]OMAR: assessment of kinetic analysis methods, test-retest reproducibility, and gender differences.
abstract: The Radiotracer [(11)C]OMAR was developed for positron emission tomography (PET) imaging of cannabinoid type-1 receptors (CB1R). The objectives of the present study were to evaluate kinetic analysis methods, determine test-retest reliability, and assess gender differences in receptor availability. Dynamic PET data were acquired in 10 human subjects, and analyzed with one-tissue (1T) and two-tissue (2T) compartment models and by the Logan and multilinear analysis (MA1) methods to estimate regional volume of distribution (VT). The 2T model inclusive of a vascular component (2TV) and MA1 were the preferred techniques. Test-retest reliability of VT was good (mean absolute deviation ~9%; intraclass correlation coefficient ~0.7). Tracer parent fraction in plasma was lower in women (P<0.0001). Cerebral uptake normalized by body weight and injected dose was higher in men by 17% (P<0.0001), but VT was significantly greater in women by 23% (P<0.0001). These findings show that [(11)C]OMAR binding can be reliably quantified by the 2T model or MA1 method and demonstrate the utility of this tracer for in vivo imaging of CB1R. In addition, results from the present study indicate that gender difference in receptor binding should be taken into consideration when [(11)C]OMAR is used to quantify CB1R availability in neuropsychiatric disorders.
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Normandin
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Ming-Qiang
authors.initials: MQ
authors.lastname: Zheng
authors.affiliation: Molecular Oncology Department, BC Cancer Agency Research Centre, Vancouver, British Columbia, Canada.
authors.forename: Kuo-Shyan
authors.initials: KS
authors.lastname: Lin
authors.affiliation: PET Facility, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: N Scott
authors.initials: NS
authors.lastname: Mason
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Shu-Fei
authors.initials: SF
authors.lastname: Lin
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Ropchan
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: David
authors.initials: D
authors.lastname: Labaree
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Shannan
authors.initials: S
authors.lastname: Henry
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Wendol A
authors.initials: WA
authors.lastname: Williams
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.affiliation: 1] Department of Psychiatry, Yale University, New Haven, Connecticut, USA [2] Molecular Imaging Program, Departments of Psychiatry and Radiology, New York University School of Medicine, New York, New York, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Neumeister
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002247:Carbon Isotopes / Q000008:administration & dosage; D002533:Cerebral Angiography / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D012727:Sex Characteristics
chemical_list: D002247:Carbon Isotopes; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1
references.citation: Biol Psychiatry. 2011 Oct 15;70(8):777-84
references.pmid: 21718968
references.citation: Annu Rev Psychol. 2013;64:21-47
references.pmid: 22804774
references.citation: Proc Natl Acad Sci U S A. 1990 Mar;87(5):1932-6
references.pmid: 2308954
references.citation: Neuroimage. 2002 Oct;17(2):825-41
references.pmid: 12377157
references.citation: Mol Psychiatry. 2013 Sep;18(9):1034-40
references.pmid: 23670490
references.citation: J Nucl Med. 2000 Dec;41(12):2083-8
references.pmid: 11138696
references.citation: Curr Pharm Des. 2014;20(13):2100-13
references.pmid: 23829370
references.citation: J Cereb Blood Flow Metab. 1990 Sep;10(5):740-7
references.pmid: 2384545
references.citation: J Cereb Blood Flow Metab. 2007 Sep;27(9):1533-9
references.pmid: 17519979
references.citation: Eur J Nucl Med Mol Imaging. 2010 May;37(5):920-33
references.pmid: 20033684
references.citation: Nature. 1993 Sep 2;365(6441):61-5
references.pmid: 7689702
references.citation: Neuroimage. 2009 Nov 1;48(2):362-70
references.pmid: 19573609
references.citation: J Nucl Med. 2006 Oct;47(10):1689-96
references.pmid: 17015906
references.citation: Curr Pharm Des. 2008;14(31):3363-83
references.pmid: 19075713
references.citation: Life Sci. 1994;54(3):159-70
references.pmid: 8289577
references.citation: Mol Pharmacol. 1988 Nov;34(5):605-13
references.pmid: 2848184
references.citation: Insight J. 2006;2006:209
references.pmid: 25364771
references.citation: Eur J Nucl Med Mol Imaging. 2010 May;37(5):917-9
references.pmid: 20358196
references.citation: Neuroimage. 2014 Jan 1;84:733-41
references.pmid: 24076222
references.citation: Br J Pharmacol. 2010 Jun;160(3):544-8
references.pmid: 20590564
references.citation: Mol Psychiatry. 2013 Aug;18(8):916-21
references.pmid: 22776901
references.citation: Eur J Nucl Med Mol Imaging. 2014 Feb;41(2):308-21
references.pmid: 24006151
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9800-5
references.pmid: 17535893
references.citation: Neuroimage. 2008 Feb 15;39(4):1533-41
references.pmid: 18077184
references.citation: Neuroimage. 2010 Oct 1;52(4):1505-13
references.pmid: 20406692
references.citation: Neuroimage. 2013 Oct 1;79:304-12
references.pmid: 23624489
references.citation: Neurobiol Aging. 2012 Mar;33(3):620.e1-8
references.pmid: 21459482
references.citation: Headache. 2012 Mar;52(3):433-40
references.pmid: 22077199
references.citation: Arch Gen Psychiatry. 2009 Feb;66(2):196-204
references.pmid: 19188542
references.citation: Nucl Med Biol. 2000 Aug;27(6):627-30
references.pmid: 11056380
references.citation: Neuroimage. 2002 Jan;15(1):273-89
references.pmid: 11771995
references.citation: Alcohol Clin Exp Res. 2012 Dec;36(12):2104-9
references.pmid: 22551199
references.citation: J Cereb Blood Flow Metab. 2002 Oct;22(10):1271-81
references.pmid: 12368666
references.citation: Nature. 1990 Aug 9;346(6284):561-4
references.pmid: 2165569
references.citation: Neuroscience. 1997 Mar;77(2):299-318
references.pmid: 9472392
references.citation: Psychoneuroendocrinology. 2010 Sep;35(8):1265-9
references.pmid: 20207489
references.citation: J Nucl Med. 2010 Jan;51(1):112-20
references.pmid: 20008988