Preclinical evaluation of a P2X7 receptor selective radiotracer: PET studies in a rat model with local overexpression of the human P2X7 receptor and in non-human primates

Ory, Dieter; Celen, Sofie; Gijsbers, Rik; Van den Haute, Chris; Postnov, Andrey; Koole, Michel; Vandeputte, Caroline; Andrés, José-Ignacio; De Angelis, Meri; Langlois, Xavier; Bhattacharya, Anindya; Schmidt, Mark; Alcazar, Jesus; Vanduffel, Wim; Letavic, Michael A; Van Laere, Koen; Verbruggen, Alfons; Debyser, Zeger; Bormans, Guy

doi:10.2967/jnumed.115.169995

Preclinical evaluation of a P2X7 receptor selective radiotracer: PET studies in a rat model with local overexpression of the human P2X7 receptor and in non-human primates

Author:

Ory, Dieter

Celen, Sofie ; Gijsbers, Rik ; Van den Haute, Chris ; Postnov, Andrey ; Koole, Michel ; Vandeputte, Caroline ; Andrés, José-Ignacio ; De Angelis, Meri ; Langlois, Xavier ; Bhattacharya, Anindya ; Schmidt, Mark ; Alcazar, Jesus ; Vanduffel, Wim ; Letavic, Michael A ; Van Laere, Koen ; Verbruggen, Alfons ; Debyser, Zeger ; Bormans, Guy

Keywords:

Science & Technology, Life Sciences & Biomedicine, Radiology, Nuclear Medicine & Medical Imaging, P2X7 receptor, neuroinflammation, PET, viral vector, non-human primate, REFERENCE TISSUE MODEL, P2X(7) RECEPTOR, PHARMACOLOGICAL CHARACTERIZATION, ANTAGONISTS, NEUROINFLAMMATION, BINDING, BRAIN, INFLAMMATION, RADIOLIGAND, MICROGLIA, Animals, Brain, Female, Humans, Macaca mulatta, Male, Metabolic Clearance Rate, Molecular Imaging, Organ Specificity, Positron-Emission Tomography, Radiopharmaceuticals, Rats, Rats, Transgenic, Rats, Wistar, Receptors, Purinergic P2X7, Reproducibility of Results, Sensitivity and Specificity, Tissue Distribution, Up-Regulation, 1103 Clinical Sciences, Nuclear Medicine & Medical Imaging, 3202 Clinical sciences

Abstract:

The P2X7 receptor (P2X7R) orchestrates (neuro)inflammation and this is the basis for an increased interest in the development of antagonists inhibiting P2X7R function in the brain. This study provides the preclinical evaluation of (11)C-JNJ-54173717, a PET tracer for the P2X7R receptor in both rats and non-human primates.