1: Nucl Med Biol. 2008 Oct;35(7):793-800. Labelling and biological evaluation of [(11)C]methoxy-Sch225336: a radioligand for the cannabinoid-type 2 receptor. Evens N, Bosier B, Lavey BJ, Kozlowski JA, Vermaelen P, Baudemprez L, Busson R, Lambert DM, Van Laere K, Verbruggen AM, Bormans GM. Laboratory for Radiopharmacy, K.U.Leuven, Leuven 3000, Belgium. INTRODUCTION: The cannabinoid type 2 receptor (CB(2) receptor) is part of the endocannabinoid system and has been suggested as mediator of a number of central and peripheral inflammatory processes. In the present study, we have synthesized N-[(1s)-1-[4-[[4-methoxy-2-[(4-[(11)C]methoxyphenyl)sulfonyl)-phenyl]sulfonyl] phenyl]ethyl]methanesulfonamide ([(11)C]methoxy-Sch225336) and evaluated this new tracer agent as a potential positron emission tomography radioligand for the in vivo visualization of CB(2) receptors. METHODS: Sch225336 was demethylated and the resulting phenol precursor was radiolabelled with a carbon-11 methyl group by methylation using [(11)C]methyl iodide, followed by purification by high-performance liquid chromatography. The log P of [(11)C]methoxy-Sch225336 and its biodistribution in normal mice were determined. Enhancement of brain uptake by inhibition of blood-brain barrier (BBB) efflux transporters was studied. Mouse plasma was analysed to quantify the formation of radiometabolites. The affinity of Sch225336 for the human cannabinoid type 1 and type 2 receptor was determined. RESULTS: [(11)C]methoxy-Sch225336 was obtained with a decay corrected radiochemical yield of about 30% and a specific activity of 88.8 GBq/mumol (end of synthesis). After intravenous injection in mice, the compound is rapidly cleared from the blood through the hepatobiliary pathway and does not show particular retention in any of the major organs. Polar metabolites were found in mouse plasma. Brain uptake was low despite the favourable log P value of 2.15, which is partly due to efflux by BBB pumps. CONCLUSION: [(11)C]methoxy-Sch225336 is a good candidate for in vivo imaging of the CB(2) receptor, although the low blood-brain barrier penetration limits its potential for central nervous system imaging. PMID: 18848664 [PubMed - indexed for MEDLINE] Related Links Characterization of peripheral human cannabinoid receptor (hCB2) expression and pharmacology using a novel radioligand, [35S]Sch225336. [J Biol Chem. 2006] PMID:16754676 Synthesis and in vivo evaluation of novel PET radioligands for imaging the endothelin-A receptor. [J Nucl Med. 2008] PMID:18703610 The PET radioligand [11C]MePPEP binds reversibly and with high specific signal to cannabinoid CB1 receptors in nonhuman primate brain. [Neuropsychopharmacology. 2008] PMID:17392732 A novel cannabinoid peripheral cannabinoid receptor-selective inverse agonist blocks leukocyte recruitment in vivo. [J Pharmacol Exp Ther. 2006] PMID:16258021 Synthesis and evaluation of dopamine D3 receptor antagonist 11C-GR218231 as PET tracer for P-glycoprotein. [J Nucl Med. 2005] PMID:16085598