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-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.
Horti
Andrew G
AG
Division of Nuclear Medicine, Department of Radiology, Johns Hopkins Medical Institutions, 600 North Wolfe Street, Baltimore, MD 21287-0816, USA. ahorti1@jhmi.edu
Gao
Yongjun
Y
Ravert
Hayden T
HT
Finley
Paige
P
Valentine
Heather
H
Wong
Dean F
DF
Endres
Christopher J
CJ
Savonenko
Alena V
AV
Dannals
Robert F
RF
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
C540311:A-836339; D002250:Carbon Radioisotopes; D043885:Receptor, Cannabinoid, CB2; D013844:Thiazoles