Preclinical evaluation and non-human primate receptor occupancy study of ¹⁸F-JNJ-64413739, a novel PET radioligand for P2X7 receptors

Abstract

Background: The P2X7 receptor is an adenosine triphosphate (ATP)-gated ion-channel, which is abundantly expressed in glial cells within the central nervous system and in the periphery. P2X7 receptor activation leads to the release of the pro-inflammatory cytokine IL-1β in the brain, and antagonism of the P2X7 receptor is a novel therapeutic strategy to dampen ATP-dependent IL-1β signaling. PET ligands for the P2X7 receptor will be not only valuable to assess central target engagement of drug candidates, but also hold promise as surrogate markers of central neuroinflammation. Herein we describe the in vitro and in vivo evaluation of ¹⁸F-JNJ-64413739, an ¹⁸F-labelled PET ligand for imaging the P2X7 receptor in the brain.