Synthesis of 11C‑Labeled Thiamine and Fursultiamine for in Vivo Molecular Imaging of Vitamin B1 and Its Prodrug Using Positron Emission Tomography
2015-06-19T00:00:00Z (GMT) by
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 9–16% and 4–10%, respectively. The radioactivities of the final injectable solutions of [11C]-1 and [11C]-2 were 400–700 and 100–250 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 97–99%, respectively. In vivo PET imaging of normal rats was illustrated by the distribution of [11C]-1 and [11C]-2 following intravenous injection.