학술논문
Imaging breast cancer using hyperpolarized carbon-13 MRI
Document Type
research-article
Author
Gallagher, Ferdia A.; Woitek, Ramona; McLean, Mary A.; Gill, Andrew B.; Garcia, Raquel Manzano; Provenzano, Elena; Riemer, Frank; Kaggie, Joshua; Chhabra, Anita; Ursprung, Stephan; Grist, James T.; Daniels, Charlie J.; Zaccagna, Fulvio; Laurent, Marie-Christine; Locke, Matthew; Hilborne, Sarah; Frary, Amy; Torheim, Turid; Boursnell, Chris; Schiller, Amy; Patterson, Ilse; Slough, Rhys; Carmo, Bruno; Kane, Justine; Biggs, Heather; Harrison, Emma; Deen, Surrin S.; Patterson, Andrew; Lanz, Titus; Kingsbury, Zoya; Ross, Mark; Basu, Bristi; Baird, Richard; Lomas, David J.; Sala, Evis; Wason, James; Rueda, Oscar M.; Chin, Suet-Feung; Wilkinson, Ian B.; Graves, Martin J.; Abraham, Jean E.; Gilbert, Fiona J.; Caldas, Carlos; Brindle, Kevin M.
Source
Proceedings of the National Academy of Sciences of the United States of America, 2020 Jan . 117(4), 2092-2098.
Subject
Language
English
ISSN
00278424
10916490
10916490
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.