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

  • Bioorg Med Chem. 2010 Jul 15;18(14):5202-7. doi: 10.1016/j.bmc.2010.05.058.
Andrew G Horti  1 ,  Yongjun Gao ,  Hayden T Ravert ,  Paige Finley ,  Heather Valentine ,  Dean F Wong ,  Christopher J Endres ,  Alena V Savonenko ,  Robert F Dannals
Affiliations
  • 1. Division of Nuclear Medicine, Department of Radiology, Johns Hopkins Medical Institutions, 600 North Wolfe Street, Baltimore, MD 21287-0816, USA. [email protected]
PMID: 20554448 DOI: 10.1016/j.bmc.2010.05.058
Abstract

Recently, A-836339 [2,2,3,3-tetramethylcyclopropanecarboxylic acid [3-(2-methoxyethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]amide] (1) was reported to be a selective CB2 Agonist with high binding affinity. Here we describe the radiosynthesis of [11C]A-836339 ([11C]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 [11C]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, [11C]1 shows specific cerebral uptake in the lipopolysaccharide (LPS)-induced mouse model of neuroinflammation and in the brain areas with Abeta 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.

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