Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 18, Issue 14, Pages 5202-5207Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2010.05.058
Keywords
Neuroinflammation; Alzheimer's disease; Cannabinoid receptor; CB2 receptor; Positron-emission tomography; PET
Funding
- NIH [MH079017]
- Division of Nuclear Medicine, Johns Hopkins School of Medicine
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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.
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