Hyperpolarized 13C Magnetic Resonance Spectroscopic Imaging of Pyruvate Metabolism in Murine Breast Cancer Models of Different Metastatic Potential

This study uses dynamic hyperpolarized [1-C-13]pyruvate magnetic resonance spectroscopic imaging (MRSI) to estimate differences in glycolytic metabolism between highly metastatic (4T1, n = 7) and metastatically dormant (4T07, n = 7) murine breast cancer models. The apparent conversion rate of pyruvate-to-lactate (k(PL)) and lactate-to-pyruvate area-under-the-curve ratio (AUC(L/P)) were estimated from the metabolite images and compared with biochemical metabolic measures and immunohistochemistry (IHC). A non-significant trend of increasing k(PL) (p = 0.17) and AUC(L/P) (p = 0.11) from 4T07 to 4T1 tumors was observed. No significant differences in tumor IHC lactate dehydrogenase-A (LDHA), monocarboxylate transporter-1 (MCT1), cluster of differentiation 31 (CD31), and hypoxia inducible factor-alpha (HIF-1 alpha), tumor lactate-dehydrogenase (LDH) activity, or blood lactate or glucose levels were found between the two tumor lines. However, AUC(L/P) was significantly correlated with tumor LDH activity (rho(spearman) = 0.621, p = 0.027) and blood glucose levels (rho(spearman) = -0.474, p = 0.042). k(PL) displayed a similar, non-significant trend for LDH activity (rho(spearman) = 0.480, p = 0.114) and blood glucose levels (rho(spearman) = -0.414, p = 0.088). Neither k(PL) nor AUC(L/P) were significantly correlated with blood lactate levels or tumor LDHA or MCT1. The significant positive correlation between AUC(L/P) and tumor LDH activity indicates the potential of AUC(L/P) as a biomarker of glycolytic metabolism in breast cancer models. However, the lack of a significant difference between in vivo tumor metabolism for the two models suggest similar pyruvate-to-lactate conversion despite differing metastatic potential.