Synthesis and biodistribution of [11C]A-836339, a new potential radioligand for PET imaging of cannabinoid type 2 receptors (CB2) |
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| Authors: | Andrew G. Horti Yongjun Gao Hayden T. Ravert Paige Finley Heather Valentine Dean F. Wong Christopher J. Endres Alena V. Savonenko Robert F. Dannals |
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| Affiliation: | 1. Division of Nuclear Medicine, Department of Radiology, Johns Hopkins Medical Institutions, 600 North Wolfe Street, Baltimore, MD 21287-0816, USA;2. Division of Medical Imaging Physics, Department of Radiology, Johns Hopkins Medical Institutions, 600 North Wolfe Street, Baltimore, MD 21287-0816, USA;3. Division of Neuropathology, Department of Pathology, Johns Hopkins Medical Institutions, 600 North Wolfe Street, Baltimore, MD 21287-0816, USA;4. Division of Neuropathology, Department of Neurology, Johns Hopkins Medical Institutions, 600 North Wolfe Street, Baltimore, MD 21287-0816, USA |
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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 Aβ 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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