Cellular release of [18F]2-fluoro-2-deoxyglucose as a function of the glucose-6-phosphatase enzyme system.
[(18)F]-2-Fluoro-2-deoxyglucose (FDG) is a glucose analog currently utilized for positron emission tomography imaging studies in humans. FDG taken up by the liver is rapidly released. This property is attributed to elevated glucose-6-phosphatase (Glc-6-Pase) activity. To characterize this issue we studied the relationship between Glc-6-Pase activity and FDG release kinetics in a cell culture system. We overexpressed the Glc-6-Pase catalytic unit in a Glc-6-Pase-deficient mouse hepatocyte (Ho-15) and in A431 tumor cell lines. Glc-6-Pase enzyme activity and FDG release rates were determined in cells transfected with the Glc-6-Pase gene (Ho-15-D3 and A431-AC3), in mock-transfected cells of both cell lines, and in wild-type mouse hepatocytes (WT10) as control. Although the highest level of Glc-6-Pase activity was measured in A431-AC3, Ho-15-D3 cells showed much faster FDG release rates. The faster FDG release correlated with the level of glucose 6-phosphate transporter (Glc-6-PT) mRNA, which was found to be expressed at higher levels in Ho-15 compared with A431 cells. Overexpression of Glc-6-PT in A431-AC3 produced a dramatic increase in FDG release compared with control cells. This study gives the first direct evidence that activity of the Glc-6-Pase complex can be quantified in vivo by measuring FDG release. Adequate levels of Glc-6-Pase catalytic unit and Glc-6-PT are required for this function. FDG-positron emission tomography may be utilized to evaluate functional status of the Glc-6-Pase complex.
Caracó
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Positron Emission Tomography and Nuclear Medicine Departments, Clinical Center, Heritable Disorders Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.
Aloj
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Chen
L Y
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Chou
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JY
Eckelman
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WC
D000818:Animals; D015152:Blotting, Northern; D020134:Catalytic Domain; D002478:Cells, Cultured; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D005952:Glucose-6-Phosphatase / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D051379:Mice; D009842:Oligopeptides; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010957:Plasmids; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection
D009842:Oligopeptides; D010455:Peptides; D012333:RNA, Messenger; D019788:Fluorodeoxyglucose F18; C085706:FLAG peptide; D005952:Glucose-6-Phosphatase