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 B-1 (thiamine) and its derivatives by positron emission tomography (PET), C-11-labeled thiamine ([C-11]-1) has been synthesized. This was carried out via a rapid, multistep synthesis consisting of Pd-0-mediated C-[C-11]methylation of a thiazole ring for 3 min and benzylation with 5-(bromomethyl)pyrimidine for 7 min. The [C-11]-1 was also converted to C-11-labeled fursultiamine ([C-11]-2), a prodrug of vitamin B-1, by disulfide formation with S-tetrahydrofurfurylthiosulfuric acid sodium salt. Characterization of [C-11]-1 and PC]-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 [C-11]-1 and [C-11]-2 were shorter than 60 and 70 min, respectively. The [C-11]CH3I-based decay-corrected radiochemical yields of [C-11]-1 and [C-11]-2 were 9-16% and 4-10%, respectively. The radioactivities of the final injectable solutions of [C-11]-1 and [C-11]-2 were 400-700 and 100-250 MBq, respectively. The radiochemical purity of both [C-11]-1 and [C-11]-2 was 99%, and the chemical purities of [C-11]-1 and [C-11]-2 were 99% and 97-99%, respectively. In vivo PET imaging of normal rats was illustrated by the distribution of [C-11]-1 and [C-11]2 following intravenous injection.