Synthesis of 11C-Labeled Thiamine and Fursultiamine for in Vivo Molecular Imaging of Vitamin B1 and Its Prodrug Using Positron Emission Tomography

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• 作者：Hisashi Doi ; Aya Mawatari ; Masakatsu Kanazawa ; Satoshi Nozaki ; Yukihiro Nomura ; Takahito Kitayoshi ; Kouji Akimoto ; Masaaki Suzuki ; Shinji Ninomiya ; Yasuyoshi Watanabe
• 刊名：Journal of Organic Chemistry
• 出版年：2015
• 出版时间：June 19, 2015
• 年：2015
• 卷：80
• 期：12
• 页码：6250-6258
• 全文大小：526K
• ISSN：1520-6904

文摘

To enable in vivo analysis of the kinetics of vitamin B₁ (thiamine) and its derivatives by positron emission tomography (PET), ¹¹C-labeled thiamine ([¹¹C]-1) has been synthesized. This was carried out via a rapid, multistep synthesis consisting of Pd⁰-mediated C-[¹¹C]methylation of a thiazole ring for 3 min and benzylation with 5-(bromomethyl)pyrimidine for 7 min. The [¹¹C]-1 was also converted to ¹¹C-labeled fursultiamine ([¹¹C]-2), a prodrug of vitamin B₁, by disulfide formation with S-tetrahydrofurfurylthiosulfuric acid sodium salt. Characterization of [¹¹C]-1 and [¹¹C]-2 showed them to be suitable for use as PET probes for in vivo pharmacokinetic and medical studies. The total durations of the preparations of [¹¹C]-1 and [¹¹C]-2 were shorter than 60 and 70 min, respectively. The [¹¹C]CH₃I-based decay-corrected radiochemical yields of [¹¹C]-1 and [¹¹C]-2 were 9鈥?6% and 4鈥?0%, respectively. The radioactivities of the final injectable solutions of [¹¹C]-1 and [¹¹C]-2 were 400鈥?00 and 100鈥?50 MBq, respectively. The radiochemical purity of both [¹¹C]-1 and [¹¹C]-2 was 99%, and the chemical purities of [¹¹C]-1 and [¹¹C]-2 were 99% and 97鈥?9%, respectively. In vivo PET imaging of normal rats was illustrated by the distribution of [¹¹C]-1 and [¹¹C]-2 following intravenous injection.