Cerebral metabolism of fluorodeoxyglucose measured with 19F NMR spectroscopy.
Brain extracts from rats given various doses of 2-fluoro-2-deoxy-D-glucose ranging from 20 to 300 mg/kg were examined with 19F NMR spectroscopy for fluorinated metabolic products and compared with the in vivo 19F spectra. Based on the analysis of these spectra and comparison with synthetic reference compounds, 2-fluoro-2-deoxy-D-glucose 6-phosphate and 2-fluoro-2-deoxy-D-mannose 6-phosphate were identified as the major metabolites present. 2-Fluoro-2-deoxy-D-6-phosphogluconate was detected only at high doses of 2-fluoro-2-deoxy-D-glucose administered, along with non-phosphorylated 2-fluoro-2-deoxy-D-glucose and 2-fluoro-2-deoxy-D-mannose. Small amounts of two other compounds, which were not identified, were also observed. Presence of the 2-fluoro-2-deoxy-D-mannose 6-phosphate is the result of 2-fluoro-2-deoxy-D-glucose 6-phosphate isomerization at the C2 position catalyzed by phosphoglucose isomerase. Results from the in vitro enzymatic reaction provide support for this hypothesis. Presence of 2-fluoro-2-deoxy-D-mannose may be the result of 2-fluoro-2-deoxy-D-glucose isomerization at the C2 position catalyzed by glucose isomerase or the result of the dephosphorylation of the 2-fluoro-2-deoxy-D-glucose 6-phosphate.
Department of Chemistry, University of Illinois, Chicago 60680.
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Wyrwicz
D000818:Animals; D001921:Brain / Q000378:metabolism*; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005461:Fluorine; D019788:Fluorodeoxyglucose F18; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D012210:Rhamnose / Q000031:analogs & derivatives / Q000378:metabolism; D014018:Tissue Distribution
D010710:Phosphates; D019788:Fluorodeoxyglucose F18; D005461:Fluorine; C017190:2-deoxy-2-fluoromannose; D003847:Deoxyglucose; D012210:Rhamnose