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

摘要

C-11-LY2795050 is a new antagonist PET radioligand for the. opioid receptor (KOR). In this study, we assessed the reproducibility of the binding parameters of C-11-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 (f(P)) measurements. The 2-tissue-compartment model and multilinear analysis-1 were applied to calculate 5 outcome measures in 14 brain regions: distribution volume (V-T), V-T normalized by f(P) (V-T/f(P)), 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 V-T value (V-T,V- CER) as the nondisplaceable V-T (V-ND) (V-ND 5 V-T,V- CER/1.17). The relative and absolute test-retest variability and intraclass correlation coefficient were evaluated for the outcome measures of C-11-LY2795050. Results: The test-retest variability of C-11-LY2795050 for V-T 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 f(P) (V-T/f(P) or BPF) did not improve the test-retest performance. Conclusion: Our results suggest that quantification of C-11-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.