Imaging breast cancer using hyperpolarized carbon-13 MRI.

Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using ¹³ C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized ¹³ C label exchange between injected [1- ¹³ C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve 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 ¹³ C MRSI was performed following injection of hyperpolarized [1- ¹³ C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes ¹³ C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized ¹³ C 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 HIF1α expression ( R = 0.83, P = 0.043). Imaging of hyperpolarized [1- ¹³ C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.
Competing Interests: Competing interest statement: A research agreement is in place between GE Healthcare and K.M.B. and F.A.G.
(Copyright © 2020 the Author(s). Published by PNAS.)