Test-Retest Reproducibility of Binding Parameters in Humans with ^sup 11^C-LY2795050, an Antagonist PET Radiotracer for the [kappa] Opioid Receptor

...-LY2795050 is a new antagonist PET radioligand for the k opioid receptor (KOR). In this study, we assessed the reproducibility of the binding parameters of ...-LY2795050 in healthy human subjects. Sixteen healthy subjects (11 men and 5 women) underwent 2 separate 90-min PET scans with arterial input function and plasma free fraction (...) measurements. The 2-tissue-compartment model and multilinear analysis-1 were applied to calculate 5 outcome measures in 14 brain regions: distribution volume (...), ... normalized by ..., 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 ... as the nondisplaceable ... The relative and absolute test-retest variability and intraclass correlation coefficient were evaluated for the outcome measures of ...-LY2795050. The test-retest variability of ...-LY2795050 for VT was no more than 10% in any region and was 12% in the amygdala. For binding potential (... and ...), the test-retest variability was good in regions of moderate and high KOR density (... > 0.4) and poor in regions of low density. Correction by ... (... or ...) did not improve the test-retest performance. Our results suggest that quantification of ...-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. (ProQuest: ... denotes formulae/symbols omitted.)