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

Andrew G. Horti, Yongjun Gao, Hayden T. Ravert, Paige Finley, Heather Valentine, Dean F. Wong, Christopher J. Endres, Alena V. Savonenko, Robert F. Dannals

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

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 Aβ amyloid plaque deposition in a mouse model of Alzheimer's disease (APPswe/PS1dE9 mice). These data establish a proof of principle that CB 2 receptors binding in the neuroinflammation and related disorders can be measured in vivo.

Original languageEnglish
Pages (from-to)5202-5207
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number14
DOIs
StatePublished - Jul 15 2010
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Cannabinoid receptor
  • CB receptor
  • Neuroinflammation
  • PET
  • Positron-emission tomography

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