Kinetic modeling of 11C-LY2795050, a novel antagonist radiotracer for PET imaging of the kappa opioid receptor in humans

¹¹C-LY2795050 is a novel kappa opioid receptor (KOR) antagonist tracer for positron emission tomography (PET) imaging. The purpose of this first-in-human study was to determine the optimal kinetic model for analysis of ¹¹C-LY2795050 imaging data. Sixteen subjects underwent baseline scans and blocking scans after oral naltrexone. Compartmental modeling and multilinear analysis-1 (MA1) were applied using the arterial input functions. Two-tissue compartment model and MA1 were found to be the best models to provide reliable measures of binding parameters. The rank order of ¹¹C-LY2795050 distribution volume (V_T) matched the known regional KOR densities in the human brain. Blocking scans with naltrexone indicated no ideal reference region for ¹¹C-LY2795050. Three methods for calculation of the nondisplaceable distribution volume (V_ND) were assessed: (1) individual V_ND estimated from naltrexone occupancy plots, (2) mean V_ND across subjects, and (3) a fixed fraction of cerebellum V_T. Approach (3) produced the lowest intersubject variability in the calculation of binding potentials (BP_ND, BP_F, and BP_P). Therefore, binding potentials of ¹¹C-LY2795050 can be determined if the specific binding fraction in the cerebellum is presumed to be unchanged by diseases and experimental conditions. In conclusion, results from the present study show the suitability of ¹¹C-LY2795050 to image and quantify KOR in humans.