Radiosynthesis of [thiocarbonyl-11C]disulfiram and its first PET study in mice

Hideki Ishii; Tomoteru Yamasaki; Joji Yui; Yiding Zhang; Masayuki Hanyu; Masanao Ogawa; Nobuki Nengaki; Atsushi B Tsuji; Yuya Terashima; Kouji Matsushima; Ming-Rong Zhang

doi:10.1016/j.bmcl.2020.126998

Radiosynthesis of [thiocarbonyl-¹¹C]disulfiram and its first PET study in mice

Bioorg Med Chem Lett. 2020 Mar 15;30(6):126998. doi: 10.1016/j.bmcl.2020.126998. Epub 2020 Jan 28.

Authors

Affiliations

¹ Department of Advanced Nuclear Medicine Sciences, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. Electronic address: ishii.hideki@qst.go.jp.
² Department of Advanced Nuclear Medicine Sciences, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
³ Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
⁴ Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Science (RIBS), Tokyo University of Science, Chiba 278-0022, Japan.
⁵ Department of Advanced Nuclear Medicine Sciences, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan. Electronic address: zhang.ming-rong@qst.go.jp.

PMID: 32014383
DOI: 10.1016/j.bmcl.2020.126998

Abstract

[Thiocarbonyl-¹¹C]disulfiram ([¹¹C]DSF) was synthesized via iodine oxidation of [¹¹C]diethylcarbamodithioic acid ([¹¹C]DETC), which was prepared from [¹¹C]carbon disulfide and diethylamine. The decay-corrected isolated radiochemical yield (RCY) of [¹¹C]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 (A_m, 0.27 GBq/μmol). On the other hand, [¹¹C]DSF was obtained in 0.4% RCY with a high A_m value (95 GBq/μmol) in the absence of carbon disulfide. The radiochemical purity of [¹¹C]DSF was always >98%. The first PET study on [¹¹C]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 A_m value of the [¹¹C]DSF sample used. In vivo metabolite analysis showed the rapid decomposition of [¹¹C]DSF in mouse plasma.

Keywords: (11)C-carbon disulfide; Diethylcarbamodithioic acid; Disulfiram; PET; Radiosynthesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carbon Disulfide / chemistry
Carbon Radioisotopes / chemistry*
Coordination Complexes / chemistry
Diethylamines / chemistry
Disulfiram / chemical synthesis*
Disulfiram / metabolism
Ditiocarb / chemistry
Gallbladder / metabolism
Iodine / chemistry
Kidney / metabolism
Ligands
Liver / metabolism
Mice
Oxidation-Reduction
Positron-Emission Tomography / methods*
Radiopharmaceuticals / chemical synthesis*
Radiopharmaceuticals / metabolism
Tissue Distribution

Substances

Carbon Radioisotopes
Coordination Complexes
Diethylamines
Ligands
Radiopharmaceuticals
Iodine
Ditiocarb
diethylamine
Carbon Disulfide
Disulfiram