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

This study uses dynamic hyperpolarized [1-C]pyruvate magnetic resonance spectroscopic imaging (MRSI) to estimate differences in glycolytic metabolism between highly metastatic (4T1, = 7) and metastatically dormant (4T07, = 7) murine breast cancer models. The apparent conversion rate of pyruvate-to-lactate (k) and lactate-to-pyruvate area-under-the-curve ratio (AUC) were estimated from the metabolite images and compared with biochemical metabolic measures and immunohistochemistry (IHC). A non-significant trend of increasing k ( = 0.17) and AUC ( = 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-α (HIF-1α), tumor lactate-dehydrogenase (LDH) activity, or blood lactate or glucose levels were found between the two tumor lines. However, AUC was significantly correlated with tumor LDH activity ( = 0.621, = 0.027) and blood glucose levels ( = -0.474, = 0.042). k displayed a similar, non-significant trend for LDH activity ( = 0.480, = 0.114) and blood glucose levels ( = -0.414, = 0.088). Neither k nor AUC were significantly correlated with blood lactate levels or tumor LDHA or MCT1. The significant positive correlation between AUC and tumor LDH activity indicates the potential of AUC 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.