Identification of 2-fluoro-2-deoxy-D-glucose metabolites by 19F(1H) hetero-RELAY.

It has been proposed that in mammalian systems the glucose analog 2-fluoro-2-deoxy-D-glucose (FDG) is phosphorylated and subsequently converted to the corresponding mannose derivative via the action of phosphoglucose isomerase. As is generally true in metabolic studies of fluorinated molecules, the fluorine spectrum alone is suggestive, without providing definitive structural evidence, while the use of 1H NMR techniques generally suffers from a lack of adequate selectivity. A 1H-19F version of the hetero-RELAY experiment has been applied to this problem. Formation of the corresponding C-6 phosphorylated 2-FDG analog with hexokinase, followed by treatment of the resulting phosphorylated products with phosphoglucose isomerase, resulted in the observation of additional 19F resonances consistent with the corresponding 2-fluoro-2-deoxy-D-mannose-6-phosphate metabolite. A more definitive product identification was obtained using the hetero-RELAY experiment, which provides a complete 19F-decoupled proton spectrum for each of the fluorinated species.