title: Metabolic pathway of 2-deoxy-2-[18F]fluoro-D-talose in mice: trapping in tissue after phosphorylation by galactokinase.
abstract: To make clear the metabolic fate of 2-deoxy-2-[18F]fluoro-D-talose ([18F]FDT) in animals, the in vivo and in vitro metabolism of non-radioactive 2-deoxy-2-fluoro-D-talose (FDT) was investigated by 19F-NMR spectroscopy. Based on the 19F-NMR spectral analyses, 2-deoxy-2-fluoro-alpha-D-talose-1-phosphate (FDT-1-P) was identified as a single metabolite in the organs of tumor-bearing mice after FDT administration (60 mg/kg). In the liver, almost all FDT was converted to FDT-1-P within 10 min after FDT injection and the phosphate form remained unchanged for at least 3 h. FDT was well converted to FDT-1-P by galactokinase in vitro. The FDT-1-P formed, however, failed to convert to a uridylate derivative by treatment with galactose-1-phosphate uridyltransferase. The observed low affinity of galactose-1-phosphate uridyltransferase for the FDT-1-P could account for the accumulation mechanism of FDT-1-P in vivo. Similar metabolic studies of [18F]FDT with radio-TLC demonstrated the [18F]FDT-1-P as a single metabolite of [18F]FDT in the mouse liver. These results indicate that [18F]FDT enters a D-galactose metabolic pathway and undergoes a metabolic trapping in the [18F]FDT-1-P form by galactokinase in the tissues such as liver and tumor. Consequently, [18F]FDT is expected to be a new radiopharmaceutical for the measurement of galactokinase activity by positron emission tomography.
authors.affiliation: Division of Radiopharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Haradahira
authors.forename: M
authors.initials: M
authors.lastname: Maeda
authors.forename: A
authors.initials: A
authors.lastname: Kato
authors.forename: Y
authors.initials: Y
authors.lastname: Kanazawa
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Torii
authors.forename: Y
authors.initials: Y
authors.lastname: Ichiya
authors.forename: K
authors.initials: K
authors.lastname: Masuda
mesh_terms: D000818:Animals; D002855:Chromatography, Thin Layer; D005260:Female; D005462:Fluorine Radioisotopes; D005686:Galactokinase / Q000378:metabolism*; D006601:Hexoses / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H; D010766:Phosphorylation; D019275:Radiopharmaceuticals / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D005462:Fluorine Radioisotopes; D006601:Hexoses; D019275:Radiopharmaceuticals; C076400:2-deoxy-2-fluorotalose; D005686:Galactokinase