title: Synthesis and biodistribution of [11C]A-836339, a new potential radioligand for PET imaging of cannabinoid type 2 receptors (CB2).
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.
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, Johns Hopkins Medical Institutions, 600 North Wolfe Street, Baltimore, MD 21287-0816, USA. ahorti1@jhmi.edu
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Horti
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Gao
authors.forename: Hayden T
authors.initials: HT
authors.lastname: Ravert
authors.forename: Paige
authors.initials: P
authors.lastname: Finley
authors.forename: Heather
authors.initials: H
authors.lastname: Valentine
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Endres
authors.forename: Alena V
authors.initials: AV
authors.lastname: Savonenko
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dannals
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D000686:Amyloidosis / Q000000981:diagnostic imaging; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes; D005260:Female; D007249:Inflammation / Q000000981:diagnostic imaging; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000032:analysis*; D013844:Thiazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics
chemical_list: C540311:A-836339; D002250:Carbon Radioisotopes; D043885:Receptor, Cannabinoid, CB2; D013844:Thiazoles