Synthesis and biodistribution of [11C] A-836339, a new potential radioligand for PET imaging of cannabinoid type 2 receptors (CB2)

Recently, A-836339 [2,2,3,3-tetramethylcyclopropanecarboxylic acid [3-(2-methoxyethyl)-4,5-dimethyl3H- thiazol-(2Z)-ylidene] amide] (1) was reported to be a selective CB2 agonist with high binding affinity. Here we describe the radiosynthesis of [C-11] A-836339 ([C-11] 1) via its desmethyl precursor as a candidate radioligand for imaging CB2 receptors with positron-emission tomography (PET). Whole body and the regional brain distribution of [C-11] 1 in control CD1 mice demonstrated that this radioligand exhibits specific uptake in the CB2-rich spleen and little specific in vivo binding in the control mouse brain. However, [C-11] 1 shows specific cerebral uptake in the lipopolysaccharide (LPS)-induced mouse model of neuroinflammation and in the brain areas with A beta amyloid plaque deposition in a mouse model of Alzheimer's disease (APPswe/PS1dE9 mice). These data establish a proof of principle that CB2 receptors binding in the neuroinflammation and related disorders can be measured in vivo. (C) 2010 Elsevier Ltd. All rights reserved.