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Synthesis of 11C‑Labeled Thiamine and Fursultiamine for in Vivo Molecular Imaging of Vitamin B1 and Its Prodrug Using Positron Emission Tomography
journal contribution
posted on 2015-06-19, 00:00 authored by Hisashi Doi, Aya Mawatari, Masakatsu Kanazawa, Satoshi Nozaki, Yukihiro Nomura, Takahito Kitayoshi, Kouji Akimoto, Masaaki Suzuki, Shinji Ninomiya, Yasuyoshi WatanabeTo 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.