title: Synthesis of (11)C-Labeled Thiamine and Fursultiamine for in Vivo Molecular Imaging of Vitamin B1 and Its Prodrug Using Positron Emission Tomography.
abstract: To enable in vivo analysis of the kinetics of vitamin B1 (thiamine) and its derivatives by positron emission tomography (PET), (11)C-labeled thiamine ([(11)C]-1) has been synthesized. This was carried out via a rapid, multistep synthesis consisting of Pd(0)-mediated C-[(11)C]methylation of a thiazole ring for 3 min and benzylation with 5-(bromomethyl)pyrimidine for 7 min. The [(11)C]-1 was also converted to (11)C-labeled fursultiamine ([(11)C]-2), a prodrug of vitamin B1, by disulfide formation with S-tetrahydrofurfurylthiosulfuric acid sodium salt. Characterization of [(11)C]-1 and [(11)C]-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 [(11)C]-1 and [(11)C]-2 were shorter than 60 and 70 min, respectively. The [(11)C]CH3I-based decay-corrected radiochemical yields of [(11)C]-1 and [(11)C]-2 were 9-16% and 4-10%, respectively. The radioactivities of the final injectable solutions of [(11)C]-1 and [(11)C]-2 were 400-700 and 100-250 MBq, respectively. The radiochemical purity of both [(11)C]-1 and [(11)C]-2 was 99%, and the chemical purities of [(11)C]-1 and [(11)C]-2 were 99% and 97-99%, respectively. In vivo PET imaging of normal rats was illustrated by the distribution of [(11)C]-1 and [(11)C]-2 following intravenous injection.
authors.affiliation: †Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies (CLST), 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Doi
authors.affiliation: †Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies (CLST), 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Mawatari
authors.affiliation: †Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies (CLST), 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Kanazawa
authors.affiliation: †Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies (CLST), 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nozaki
authors.affiliation: ‡Takeda Pharmaceutical Company Limited, 12-10 Nihonbashi 2-Chome, Chuo-ku, Tokyo 103-8668, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Nomura
authors.affiliation: ‡Takeda Pharmaceutical Company Limited, 12-10 Nihonbashi 2-Chome, Chuo-ku, Tokyo 103-8668, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Kitayoshi
authors.affiliation: ‡Takeda Pharmaceutical Company Limited, 12-10 Nihonbashi 2-Chome, Chuo-ku, Tokyo 103-8668, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Akimoto
authors.affiliation: §National Center for Geriatrics and Gerontology, 35 Gengo, Morioka, Obu, Aichi 474-8511, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: ‡Takeda Pharmaceutical Company Limited, 12-10 Nihonbashi 2-Chome, Chuo-ku, Tokyo 103-8668, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ninomiya
authors.affiliation: †Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies (CLST), 6-7-3 Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes / Q000737:chemistry*; D005666:Fursultiamin / Q000138:chemical synthesis* / Q000737:chemistry; D007275:Injections, Intravenous / Q000379:methods; D057054:Molecular Imaging; D049268:Positron-Emission Tomography; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D051381:Rats; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013831:Thiamine / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C000605695:5-(bromomethyl)pyrimidine; D002250:Carbon Radioisotopes; D011355:Prodrugs; D011743:Pyrimidines; D013438:Sulfhydryl Compounds; D005666:Fursultiamin; D013831:Thiamine