title: Parametric Imaging and Test-Retest Variability of ¹¹C-(+)-PHNO Binding to D₂/D₃ Dopamine Receptors in Humans on the High-Resolution Research Tomograph PET Scanner.
abstract: (11)C-(+)-4-propyl-9-hydroxynaphthoxazine ((11)C-(+)-PHNO) is an agonist radioligand for imaging dopamine D2 and D3 receptors in the human brain with PET. In this study we evaluated the reproducibility of (11)C-(+)-PHNO binding parameters using a within-day design and assessed parametric imaging methods.
  
  
  METHODS
  Repeated studies were performed in 8 subjects, with simultaneous measurement of the arterial input function and plasma free fraction. Two (11)C-(+)-PHNO scans for the same subject were separated by 5.4 ± 0.7 h. After compartment models were evaluated, (11)C-(+)-PHNO volumes of distribution (V(T)) and binding potentials relative to the concentration of tracer in plasma (BP(P)), nondisplaceable tracer in tissue (BP(ND)), and free tracer in tissue (BP(F)) were quantified using the multilinear analysis MA1 method, with the cerebellum as the reference region. Parametric images of BP(ND) were also computed using the simplified reference tissue model (SRTM) and SRTM2.
  
  
  RESULTS
  The test-retest variability of (11)C-(+)-PHNO BP(ND) was 9% in D2-rich regions (caudate and putamen). Among D3-rich regions, variability was low in the pallidum (6%) but higher in substantia nigra (19%), thalamus (14%), and hypothalamus (21%). No significant mass carry-over effect was observed in D3-rich regions, although a trend in BP(ND) was present in the substantia nigra (-14% ± 15%). Because of the relatively fast kinetics, low-noise BP(ND) parametric images were obtained with both SRTM and SRTM2 without spatial smoothing.
  
  
  CONCLUSIONS
  (11)C-(+)-PHNO can be used to compute low-noise parametric images in both D2- and D3-rich regions in humans.
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut jean-dominique.gallezot@yale.edu.
authors.forename: Jean-Dominique
authors.initials: JD
authors.lastname: Gallezot
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Ming-Qiang
authors.initials: MQ
authors.lastname: Zheng
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Keunpoong
authors.initials: K
authors.lastname: Lim
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut.
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.
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 Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; and.
authors.forename: David
authors.initials: D
authors.lastname: Matuskey
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut Department of Radiology and Psychiatry, New York University School of Medicine, New York, New York.
authors.forename: Yu-Shin
authors.initials: YS
authors.lastname: Ding
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; and.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Malison
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D010078:Oxazines / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000295:instrumentation*; D011485:Protein Binding; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D010078:Oxazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C042631:naxagolide
keywords: agonist; dopamine D2 receptor; dopamine D3 receptor; positron emission tomography; test–retest study
references.citation: Neuroimage. 2011 Jan 1;54(1):264-77
references.pmid: 20600980
references.citation: Eur J Nucl Med Mol Imaging. 2013 Apr;40(4):574-9
references.pmid: 23238524
references.citation: Biol Psychiatry. 2006 Mar 1;59(5):389-94
references.pmid: 16373068
references.citation: J Med Chem. 2005 Jun 16;48(12):4153-60
references.pmid: 15943487
references.citation: J Cereb Blood Flow Metab. 2011 Jan;31(1):155-65
references.pmid: 20442726
references.citation: J Cereb Blood Flow Metab. 2002 Oct;22(10):1271-81
references.pmid: 12368666
references.citation: J Pharmacol Exp Ther. 1994 Jan;268(1):417-26
references.pmid: 8301582
references.citation: Synapse. 2012 Jun;66(6):489-500
references.pmid: 22213512
references.citation: Neuroimage. 2013 Mar;68:119-32
references.pmid: 23207573
references.citation: Synapse. 2009 Jul;63(7):574-84
references.pmid: 19301416
references.citation: J Cereb Blood Flow Metab. 2001 Sep;21(9):1034-57
references.pmid: 11524609
references.citation: Neuroimage. 1996 Dec;4(3 Pt 1):153-8
references.pmid: 9345505
references.citation: J Cereb Blood Flow Metab. 2007 Apr;27(4):857-71
references.pmid: 17033687
references.citation: Neuropsychopharmacology. 2011 Mar;36(4):887-95
references.pmid: 21178982
references.citation: J Cereb Blood Flow Metab. 2007 Sep;27(9):1533-9
references.pmid: 17519979
references.citation: J Cereb Blood Flow Metab. 1994 Nov;14(6):995-1010
references.pmid: 7929663
references.citation: J Cereb Blood Flow Metab. 2002 Dec;22(12):1440-52
references.pmid: 12468889
references.citation: Int J Neuropsychopharmacol. 2010 Apr;13(3):289-90
references.pmid: 20149269
references.citation: Synapse. 2006 Dec 1;60(7):485-95
references.pmid: 16952157
references.citation: Psychol Bull. 1979 Mar;86(2):420-8
references.pmid: 18839484
references.citation: Neuropsychopharmacology. 2008 Jan;33(2):279-89
references.pmid: 17406650
references.citation: Mol Imaging. 2013 Mar-Apr;12(2):77-82
references.pmid: 23415395