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J Nucl Med. 2015 Feb;56(2):243-8. doi: 10.2967/jnumed.114.147975. Epub 2015 Jan 15.

Test-retest reproducibility of binding parameters in humans with 11C-LY2795050, an antagonist PET radiotracer for the κ opioid receptor.

Author information

  • 1PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut mika.naganawa@yale.edu.
  • 2PET Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut.
  • 3Eli Lilly and Co., Indianapolis, Indiana; and.
  • 4Department of Psychiatry and Radiology, New York University School of Medicine, New York, New York.

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.

CONCLUSION:

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.

KEYWORDS:

brain imaging; kappa opioid receptor; positron emission tomography; test–retest reproducibility

PMID:
25593119
PMCID:
PMC4322754
DOI:
10.2967/jnumed.114.147975
[PubMed - indexed for MEDLINE]
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