N-[(1s)-1-[4-[[4-methoxy-2-[(4-[11C]methoxyphenyl)sulfonyl]-phenyl]sulfonyl]phenyl]ethyl]methanesulfonamide

Excerpt

There are two known sub-types of the G-protein–coupled cannabinoid receptors, CB1R and CB2R, and they are believed to participate in many physiological processes such as neurotransmission, energy homeostasis, and the control of immune cell function (1). The CB1R are found primarily in the brain, whereas the CB2R are expressed predominantly on immune cells (2). However, the CB2R were shown recently to be expressed on brain neurons as well and were reported to have a role in the development of conditions such as drug abuse and depression (3). The modulation of CB2R expression has been reported in astrocytic tumors, atherosclerotic and amyloid plaques, and demyelination plaques observed in multiple sclerosis (4). A variety of CB2R antagonists and agonists are commercially available, and some agonists have been shown to induce apoptosis in various tumor cell types and are used to treat pain and inflammation observed during neuropathy, cancer, multiple sclerosis, etc (5). In addition, some agonists have been used for the management of depression, attention-deficit hyperactivity, and anxiety disorders (5).

A few tritiated ligands have been used to investigate the CB2R under in vitro conditions; however, due to low specific activity and a lack of receptor selectivity, these radioligands are not considered entirely suitable to study CB1R and CB2R (4). Recently, the ³⁵S-labeled compound [³⁵S]Sch225336 (N-[(1s)-1-[4-[[4-methoxy-2-[(4-[³⁵S]methoxyphenyl)sulfonyl]-phenyl]sulfonyl] phenyl]ethyl]methanesulfonamide), with a high specific activity, was shown to specifically bind and act as a reverse agonist for the human CB2R (hCB2R) in in vitro binding studies (6). A near-infrared (NIR)–labeled dye that specifically bound to the CB2R was developed by Bai et al. for in vitro fluorescence imaging of the receptor (7). In addition, several clinical trials approved by the United States Food and Drug Administration are in progress to evaluate the use of positron emission tomography (PET) for the imaging of CB1R. Because no suitable radiolabeled ligand is available for the noninvasive study and investigation of the CB2R, the ¹¹C-labeled compound [¹¹C]methoxy-Sch225336 was synthesized and evaluated by Evens et al. (4) in miceas a potential PET imaging agent.