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Synthesis and biodistribution of [11C]A-836339, a new potential radioligand for PET imaging of cannabinoid type 2 receptors (CB2).
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2010 Jul 15; Vol. 18 (14), pp. 5202-7. Date of Electronic Publication: 2010 May 25. - Publication Year :
- 2010
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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.<br /> (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)
- Subjects :
- Amyloidosis diagnostic imaging
Animals
Brain diagnostic imaging
Brain metabolism
Carbon Radioisotopes
Female
Inflammation diagnostic imaging
Male
Mice
Receptor, Cannabinoid, CB2 agonists
Thiazoles pharmacokinetics
Alzheimer Disease diagnostic imaging
Positron-Emission Tomography methods
Receptor, Cannabinoid, CB2 analysis
Thiazoles chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 18
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 20554448
- Full Text :
- https://doi.org/10.1016/j.bmc.2010.05.058