Evaluation of the Agonist PET Radioligand11CGR103545 to Image Kappa Opioid Receptor inHumans: Kinetic Model Selection Test-Retest Reproducibility and ReceptorOccupancy by the Antagonist PF-04455242

摘要

IntroductionKappa opioid receptors (KOR) are implicated in several brain disorders. In this report, a first-in-human Positron Emission Tomography (PET) study was conducted with the potent and selective KOR agonist tracer, [¹¹C], to determine an appropriate kinetic model for analysis of PET imaging data and assess the test-retest reproducibility of model-derived binding parameters. The non-displaceable distribution volume (VND) was estimated from a blocking study with naltrexone. In addition, KOR occupancy of PF-04455242, a selective KOR antagonist that is active in preclinical models of depression, was also investigated.