Preclinical evaluation of [11C]NE40, a type 2 cannabinoid receptor PET tracer

Introduction: Up-regulation of the type 2 cannabinoid receptor (CB2R) has been reported in (neuro)inflammatory diseases. In this study, we report the preclinical evaluation of [C-11]NE40 as positron emission tomography (PET) radioligand for visualization of the CB2R. Methods: The selectivity of NE40 for CB2R and its toxicity and mutagenicity were determined. [C-11]NE40 was evaluated by biodistribution and autoradiography studies in normal rats and a microPET study in normal mice, rats and a rhesus monkey. Specific in vivo binding of [C-11]NE40 to human CB2R (hCB(2)R) was studied in a rat model with hCB(2)R overexpression. Results: [C-11]NE40 shows specific CB2R binding in the spleen and blood of normal rats and high brain uptake in rhesus monkey. [C-11]NE40 showed specific and reversible binding to hCB(2)R in vivo in a rat model with local hCB(2)R overexpression. Conclusions: [C-11]NE40 shows favorable characteristics as radioligand for in vivo visualization of the CB2R and is a promising candidate for hCB(2)R PET imaging. (C) 2012 Elsevier Inc. All rights reserved.