Metabolic pathway of 2-deoxy-2-[18F]fluoro-D-talose in mice: trapping in tissue after phosphorylation by...

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.