Imaging breast cancer using hyperpolarized carbon-13 MRI
Ferdia A. Gallagher, Ramona Woitek, Mary A. McLean, Andrew B. Gill, Raquel Manzano García, Elena Provenzano, Frank Riemer, Joshua Kaggie, Anita Chhabra, Stephan Ursprung, James T. Grist, Charlie J. Daniels, Fulvio Zaccagna, Marie‐Christine Laurent, M. Locke, Sarah Hilborne, Amy Frary, Turid Torheim, Chris Boursnell, Amy Schiller, Ilse Patterson, Rhys Slough, Bruno Carmo, Justine M. Kane, Heather Biggs, Emma Harrison, Surrin S. Deen, Andrew J. Patterson, Titus Lanz, Zoya Kingsbury, Mark T. Ross, Bristi Basu, Richard D. Baird, David J. Lomas, Evis Sala, James Wason, Oscar M. Rueda, Suet‐Feung Chin, Ian B. Wilkinson, Martin J. Graves, Jean Abraham, Fiona J. Gilbert, Carlos Caldas, Kevin M. Brindle
Abstract
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.