Glycolysis as a metabolic marker in orthotopic breast cancer, monitored by in vivo (13)C MRS.
Enhanced glycolysis represents a striking feature of cancers and can therefore serve to indicate a malignant transformation. We have developed a noninvasive, quantitative method to characterize tumor glycolysis by monitoring (13)C-labeled glucose and lactate with magnetic resonance spectroscopy. This method was applied in MCF7 human breast cancer implanted in the mammary gland of female CD1-NU mice and was further employed to assess tumor response to hormonal manipulation with the antiestrogen tamoxifen. Analysis of the kinetic data based on a unique physiological-metabolic model yielded the rate parameters of glycolysis, glucose perfusion, and lactate clearance in the tumor, as well as glucose pharmacokinetics in the plasma. Treatment with tamoxifen induced a twofold reduction in the rate of glycolysis and of lactate clearance but did not affect the other parameters. This metabolic monitoring can thus serve to evaluate the efficacy of new selective estrogen receptor modulators and may be further extended to improve diagnosis and prognosis of breast cancer.
Rivenzon-Segal
Dalia
D
Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
Margalit
Raanan
R
Degani
Hadassa
H
D000818:Animals; D015415:Biomarkers; D001943:Breast Neoplasms / Q000378:metabolism*; D002247:Carbon Isotopes; D004195:Disease Models, Animal; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics; D006019:Glycolysis; D006801:Humans; D019344:Lactic Acid / Q000493:pharmacokinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D008954:Models, Biological; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000637:transplantation
D015415:Biomarkers; D002247:Carbon Isotopes; D019344:Lactic Acid; D005947:Glucose