Introduction: Hypoxia can stimulate (18)F-fluorodeoxyglucose (FDG) uptake in cultured cells. A better understanding of the underlying molecular mechanism is required to determine the value of FDG for studying tumour hypoxia.
Methods: The effect of hypoxia on FDG uptake, and key proteins involved in glucose transport and glycolysis, was studied in MCF7 and MDA231 breast cancer cell lines.
Results: Hypoxia induced a dose- and time-dependent increase in FDG uptake. The FDG increase was transient, suggesting that FDG uptake is only likely to be increased by acute hypoxia (<24 h). Molecular analysis indicated that hypoxia upregulated glut1 and 6-phosphofructo-2-kinase, key proteins involved in regulating glucose transport and glycolysis, and that these changes were induced by Hypoxia-Inducible factor 1 (HIF1) upregulation and/or AMP-activated protein kinase activation.
Conclusions: FDG may provide useful information about the oxygenation status of cells in hypoxic regions where HIF1 upregulation is hypoxia-driven.
Keywords: (18)F-Fluorodeoxyglucose; (18)F-Fluoromisonidazole; 6-phosphofructo-2-kinase; AMP-activated protein kinase; AMPK; DTT; Dithiothreitol; FDG; FMISO; Fluorodeoxyglucose; HIF1; HK2; Hexokinase 2; Hypoxia; Hypoxia-inducible factor 1; MDA231; MDAMB231; OMG; Oncology, Positron Emission Tomography; PBS; PET; PFK2; Phosphate buffered saline; Positron Emission Tomography; [(3)H]-o-methylglucose.
Copyright © 2013 Elsevier Inc. All rights reserved.