Imaging breast cancer using hyperpolarized carbon-13 MRI

Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using C-13 magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized C-13 label exchange between injected [1-C-1(3)]pyruvate and the endogenous tumor lactate pool. Treatment-naive breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2-), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2- invasive lobular carcinoma (ILC). Dynamic C-13 MRSI was performed following injection of hyperpolarized [1(13)C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes C-13 label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1 alpha), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized C-13 MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean +/- SD: 0.145 +/- 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1 alpha expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-C-13]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.