Development and In Vivo Evaluation of a κ-Opioid Receptor Agonist as a PET Radiotracer with Superior Imaging Characteristics.

ABSTRACT: Studies have shown κ-opioid receptor (KOR) abnormalities in addictive disorders, other central nervous system diseases, and Alzheimer's disease. We have developed the first set of agonist ¹¹C-GR103545 and antagonist ¹¹C-LY2795050 radiotracers for PET imaging of KOR in humans. Nonetheless, ¹¹C-GR103545 displays protracted uptake kinetics and is not an optimal radiotracer. Here, we report the development and evaluation of ¹¹C-methyl-(R)-4-(2-(3,4-dichlorophenyl)acetyl)-3-((diethylamino)methyl)piperazine-1-carboxylate (¹¹C-EKAP) and its comparison with ¹¹C-GR103545. Methods: EKAP was synthesized and assayed for in vitro binding affinities and then radiolabeled. PET studies were performed on rhesus monkeys.

SUBMITTER: Li S 

PROVIDER: S-EPMC6604690 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature