Metabolic Imaging: A Link between Lactate Dehydrogenase A, Lactate, and Tumor Phenotype.
PURPOSE: We compared the metabolic profiles and the association between LDH-A expression and lactate production in two isogenic murine breast cancer cell lines and tumors (67NR and 4T1). These cell lines were derived from a single mammary tumor and have different growth and metabolic phenotypes. EXPERIMENTAL DESIGN: LDH-A expression, lactate concentration, glucose utilization, and oxygen consumption were measured in cells, and the potential relationship between tumor lactate levels [measured by magnetic resonance spectroscopic imaging (MRSI)] and tumor glucose utilization [measured by [(18)F]2-deoxy-2-fluoro-d-glucose positron emission tomography ([(18)F]FDG-PET)] was assessed in orthotopic breast tumors derived from these cell lines. RESULTS: We show a substantial difference in LDH-A expression between 67NR and 4T1 cells under normoxia and hypoxia. We also show that small orthotopic 4T1 tumors generate 10-fold more lactate than corresponding 67NR tumors. The high lactate levels in small primary 4T1 tumors are associated with intense pimonidazole staining (a hypoxia indicator). Less-intense hypoxia staining was observed in the larger 67NR tumors and is consistent with the gradual increase and plateau of lactate concentration in enlarging 67NR tumors. CONCLUSIONS: Lactate-MRSI has a greater dynamic range than [(18)F]FDG-PET and may be a more sensitive measure with which to evaluate the aggressive and metastatic potential of primary breast tumors. Clin Cancer Res; 17(19); 6250-61. ©2011 AACR.[1]References
- Metabolic Imaging: A Link between Lactate Dehydrogenase A, Lactate, and Tumor Phenotype. Serganova, I., Rizwan, A., Ni, X., Thakur, S.B., Vider, J., Russell, J., Blasberg, R., Koutcher, J.A. Clin. Cancer Res. (2011) [Pubmed]
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