title: Test-retest reproducibility of binding parameters in humans with 11C-LY2795050, an antagonist PET radiotracer for the κ opioid receptor.
abstract: (11)C-LY2795050 is a new antagonist PET radioligand for the κ opioid receptor (KOR). In this study, we assessed the reproducibility of the binding parameters of (11)C-LY2795050 in healthy human subjects.
  
  
  METHODS
  Sixteen healthy subjects (11 men and 5 women) underwent 2 separate 90-min PET scans with arterial input function and plasma free fraction (fP) measurements. The 2-tissue-compartment model and multilinear analysis-1 were applied to calculate 5 outcome measures in 14 brain regions: distribution volume (VT), VT normalized by fP (VT/fP), and 3 binding potentials (nondisplaceable binding potential, binding potential relative to total plasma concentration, and binding potential relative to free plasma concentration: BPND, BPP, BPF, respectively). Since KOR is distributed ubiquitously throughout the brain, there are no suitable reference regions. We used a fixed fraction of individual cerebellar VT value (VT,CER) as the nondisplaceable VT (VND) (VND = VT,CER/1.17). The relative and absolute test-retest variability and intraclass correlation coefficient were evaluated for the outcome measures of (11)C-LY2795050.
  
  
  RESULTS
  The test-retest variability of (11)C-LY2795050 for VT was no more than 10% in any region and was 12% in the amygdala. For binding potential (BPND and BPP), the test-retest variability was good in regions of moderate and high KOR density (BPND > 0.4) and poor in regions of low density. Correction by fP (VT/fP or BPF) did not improve the test-retest performance.
  
  
  CONCLUSIONS
  Our results suggest that quantification of (11)C-LY2795050 imaging is reproducible and reliable in regions with moderate and high KOR density. Therefore, we conclude that this first antagonist radiotracer is highly useful for PET studies of KOR.
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut mika.naganawa@yale.edu.
authors.forename: Mika
authors.initials: M
authors.lastname: Naganawa
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: Shannan
authors.initials: S
authors.lastname: Henry
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Nabulsi
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: Jim
authors.initials: J
authors.lastname: Ropchan
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.
authors.forename: Soheila
authors.initials: S
authors.lastname: Najafzadeh
authors.affiliation: PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Michael
authors.initials: M
authors.lastname: Kapinos
authors.affiliation: Eli Lilly and Co., Indianapolis, Indiana; and.
authors.forename: Johannes
authors.initials: J
authors.lastname: Tauscher
authors.affiliation: Department of Psychiatry and Radiology, New York University School of Medicine, New York, New York.
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.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
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
mesh_terms: D000328:Adult; D001549:Benzamides; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D015203:Reproducibility of Results; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C570402:3-chloro-4-(4-((2-(3-pyridyl)pyrrolidin-1-yl)methyl)phenoxy)benzamide; D001549:Benzamides; D002250:Carbon Radioisotopes; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017473:Receptors, Opioid, kappa
keywords: brain imaging; kappa opioid receptor; positron emission tomography; test–retest reproducibility