量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
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Objectives
There exist carrier-mediated systems for actively transporting thiocyanate from the brain to the blood, causing the low concentration of thiocyanate in the brain in addition to the limited permeability of the blood-brain barrier. Evaluation of the in vivo efflux of thiocyanate will contribute to elucidating the physiological and biological implication of the efflux systems in the brain. However, the currently available methods are limited to invasive evaluation by microinjection of radioactive thiocyanate into the brain. Here, we present the radiosynthesis of the organic [11C]thiocyanates for imaging thiocyanate efflux from the brain. Based on the metabolite extrusion method [1], we designed candidate protracers: methyl [11C]thiocyanate ([11C]MeT), benzyl [11C]thiocyanate ([11C]BnT), phenyl [11C]thiocyanate ([11C]PhT), 2,4-dinitrophenyl [11C]thiocyanate ([11C]DNPT), and 6-[11C]thiocyanatopurine derivative ([11C]TP).
Methods
The 11C-labeled candidates were synthesized via the reaction of halide-precursor with [11C]thiocyanate or the reaction of disulfide-precursor with [11C]cyanide. All radiochemical yields (RCYs) were determined by radio-HPLC analysis of the crude product. The effects of reaction time, solvents (methanol, acetonitrile, N,N-dimethylformamide, acetone, or tetrahydrofuran), and reaction temperature on RCYs of the 11C-labled candidates were investigated.
Results
In either acetone, N,N-dimethylformamide, or tetrahydrofuran, methyl iodide reacted with [11C]thiocyanate to provide moderate to high RCY of the product under short-reaction time at 80°C. Thiocyanation of benzyl bromide with[11C]thiocyanate proceeded under the same conditions. By contrast, the conversion of halide-precursors to [11C]Ph, [11C]DNPT, [11C]TP was poor. In the presence of CuSO4, [11C]DNPT and [11C]TP were successfully produced at 150°C in high RCY (80–90%) and moderate RCY (60%), respectively. The conversion to [11C]PhT was still poor in the presence of CuSO4; however, the reaction of the disulfide-precursor with [11C]cyanide provided moderate RCY of [11C]PhT. This reaction also provided [11C]TP in high RCY.
Conclusions
The candidates, [11C]MeT, [11C]BnT, [11C]PhT, [11C]DNPT, and [11C]TP, were successfully synthesized by either the reaction of halide-precursors with [11C]thiocyanate or disulfide-precursors with [11C]cyanide. Further in vivo studies are in progress.
Synthesis of PET tracers for imaging of thiocyanate efflux from the brain
