Presentation Radiosynthesis of [11C]disulfiram and its first in vivo PET studies

Ishii, Hideki  ,  Yui, Joji  ,  Zhang, Yiding  ,  Yamasaki, Tomoteru  ,  Hanyu, Masayuki  ,  Ogawa, Masanao  ,  Nengaki, Nobuki  ,  Tsuji, Atsushi  ,  Ming-Rong, Zhang

2017-05-15
Description
Objectives: Disulfiram (DSF) has been widely used to treat alcoholism for more than half a century and recent studies suggest that DSF may have potential therapeutic effect for several cancers. However, the detail reaction mechanism for the anti-cancer effect of DSF is still not clear. Therefore, the development of [11C]DSF and its in vivo and in vitro studies might be helpful for the understanding of the role of DSF. Here we present the first synthesis of [11C]DSF using [11C]carbon disulfide ([11C]CS2) as a labelling agent. Methods: [11C]DSF was synthesized via iodine (I2) oxidation of [11C]diethylcarbamodithioic acid ([11C]DETC), which was prepared by the reaction of [11C]CS2 and diethylamine in acetonitrile (MeCN) at room temperature (r.t.)Results: The (decay-corrected isolated) radiochemical yield (RCY) of [11C]DSF was greatly affected by the addition of non-radioactive carbon disulfide (CS2). In the presence of CS2, RCY was increased up to 22% with low molar radioactivity (0.27 GBq/mol). On the other hand, in the absence of CS2, [11C]DSF was obtained in 0.4% RCY with high molar radioactivity (95 GBq/mol). The radiochemical purities (determined by radio-HPLC analysis of the isolated product) of [11C]DSF were always greater than 98%. The first PET study of [11C]DSF was performed on mice. High uptake of radioactivity in the liver, kidney and gallbladder were observed and the metabolite analysis of mouse serum showed the rapid decomposition of [11C]DSF.Conclusions: [11C]DSF was successfully synthesized by the reaction of [11C]CS2 with diethylamine followed by I2 oxidation. Regardless of the molar radioactivity, PET studies of [11C]DSF showed similar uptake in mouse organ and rapid decomposition in serum.
22nd International symposium on radiopharmaceutical science (ISRS)

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