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

To enable in vivo analysis of the kinetics of vitamin B₁ (thiamine) and its derivatives by positron emission tomography (PET), ¹¹C-labeled thiamine ([¹¹C]-<b>1</b>) has been synthesized. This was carried out via a rapid, multistep synthesis consisting of Pd⁰-mediated <i>C</i>-[¹¹C]­methylation of a thiazole ring for 3 min and benzylation with 5-(bromomethyl)­pyrimidine for 7 min. The [¹¹C]-<b>1</b> was also converted to ¹¹C-labeled fursultiamine ([¹¹C]-<b>2</b>), a prodrug of vitamin B₁, by disulfide formation with <i>S</i>-tetrahydrofurfurylthiosulfuric acid sodium salt. Characterization of [¹¹C]-<b>1</b> and [¹¹C]-<b>2</b> 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]-<b>1</b> and [¹¹C]-<b>2</b> were shorter than 60 and 70 min, respectively. The [¹¹C]­CH₃I-based decay-corrected radiochemical yields of [¹¹C]-<b>1</b> and [¹¹C]-<b>2</b> were 9–16% and 4–10%, respectively. The radioactivities of the final injectable solutions of [¹¹C]-<b>1</b> and [¹¹C]-<b>2</b> were 400–700 and 100–250 MBq, respectively. The radiochemical purity of both [¹¹C]-<b>1</b> and [¹¹C]-<b>2</b> was 99%, and the chemical purities of [¹¹C]-<b>1</b> and [¹¹C]-<b>2</b> were 99% and 97–99%, respectively. In vivo PET imaging of normal rats was illustrated by the distribution of [¹¹C]-<b>1</b> and [¹¹C]-<b>2</b> following intravenous injection