Two-compartment model for determination of glycolytic rates of solid tumors by in vivo 13C NMR spectroscopy.
Carbon-13 NMR spectroscopy of 13C enriched substrates is useful for non-invasively determining metabolic fluxes of cells and tissues. Our study demonstrates that for RIF-1 tumor cells, examined under monolayer culture with continuous perfusion and also grown as solid subcutaneously (sc) implanted tumors in vivo, the levels of intracellular glucose and intermediates of the glycolytic pathway are below the level of detection by NMR spectroscopy. For these tumors, glucose transport into the cell is the most probable rate limiting step of the glycolytic pathway. Under these limiting conditions a simple two-compartment model of glycolysis applies. This model yields two parameters: the average rate of glycolysis and the rate of lactate clearance through the vasculature. For the RIF-1 tumor these parameters were 0.022 +/- 0.01 and 0.034 +/- 0.006 min(-1), respectively.
Artemov
D
D
Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2195, USA.
Bhujwalla
Z M
ZM
Pilatus
U
U
Glickson
J D
JD
D000818:Animals; D002247:Carbon Isotopes; D004195:Disease Models, Animal; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D019344:Lactic Acid / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010758:Phosphorus; D011522:Protons; D012878:Skin Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002247:Carbon Isotopes; D011522:Protons; D010758:Phosphorus; D019344:Lactic Acid; D005947:Glucose