Several antagonists of the P2X7R have been radiolabeled with 11C for evaluation of the receptor expression and function as shown in Figure 6. The selective P2X7R antagonist A-740003 (IC50 = 18 nM, rP2X7R and IC50 = 40 nM, hP2X7R) was radiolabeled with 11C to produce [11C]A-740003,205 but showed low biodistribution and poor brain permeability.205 The first brain penetrable 11C PET radioligand for quantification of P2X7R expression in the brain was [11C]JNJ-54173717. This tracer showed high potency in humanized rat P2X7R (IC50 = 4.2 nM, hP2X7R)206 and excellent uptake in the hP2X7R overexpressing striatum area that was reduced by pretreatment with nonradioactive antagonists JNJ-54173717 and JNJ-42253432, suggesting selective P2X7R binding of this radiotracer in the brain.24 Additionally, [11C]JNJ-54173717 displayed high brain uptake in rhesus monkey, an indication of BBB penetrability to study receptor expression levels in neurodegenerative disorders in humans.206 Another potent P2X7 receptor antagonist, benzamide GSK1482160 was also radiolabeled with 11C to produce PET radioligand [11C]GSK1482160 (Ki = 2.63 nM, IC50 = 3 nM, hP2X7 and Kd = 1.15 ± 0.12 nM, hP2X7R).207-209 Evaluation of [11C]GSK1482160 in mouse model of
