Radiosynthesis of [thiocarbonyl-11C]disulfiram and its first PET study in mice. Issue 6 (15th March 2020)

• Record Type: Journal Article
• Authors: Ishii, Hideki; Yamasaki, Tomoteru; Yui, Joji; Zhang, Yiding; Hanyu, Masayuki; Ogawa, Masanao; Nengaki, Nobuki; Tsuji, Atsushi B.; Terashima, Yuya; Matsushima, Kouji; Zhang, Ming-Rong
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 6(2020)
• Publication Date: 2020-03-15
• Subjects: Disulfiram -- PET -- 11C-carbon disulfide -- Radiosynthesis -- Diethylcarbamodithioic acid; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.126998
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: [ Thiocarbonyl - 11 C]disulfiram ([ 11 C]DSF) was synthesized via iodine oxidation of [ 11 C]diethylcarbamodithioic acid ([ 11 C]DETC), which was prepared from [ 11 C]carbon disulfide and diethylamine. The decay-corrected isolated radiochemical yield (RCY) of [ 11 C]DSF was greatly affected by the addition of unlabeled carbon disulfide. In the presence of carbon disulfide, the RCY was increased up to 22% with low molar activity ( Am, 0.27 GBq/μmol). On the other hand, [ 11 C]DSF was obtained in 0.4% RCY with a high Am value (95 GBq/μmol) in the absence of carbon disulfide. The radiochemical purity of [ 11 C]DSF was always >98%. The first PET study on [ 11 C]DSF was performed in mice. A high uptake of radioactivity was observed in the liver, kidneys, and gallbladder. The uptake level and distribution pattern in mice were not significantly affected by the Am value of the [ 11 C]DSF sample used. In vivo metabolite analysis showed the rapid decomposition of [ 11 C]DSF in mouse plasma.