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| Proceedings of the National Academy of Sciences of the United States of America. 2020 Jan 21. pii: 1913841117. doi: 10.1073/pnas.1913841117 |
| Imaging breast cancer using hyperpolarized carbon-13 MRI. |
| Gallagher FA1, Woitek R2, McLean MA3, Gill AB4, Manzano Garcia R5, Provenzano E6, Riemer F7, Kaggie J8, Chhabra A9, Ursprung S10, Grist JT11, Daniels CJ12, Zaccagna F13, Laurent MC14, Locke M15, Hilborne S16, Frary A17, Torheim T18, Boursnell C19, Schiller A20, Patterson I21, Slough R22, Carmo B23, Kane J24, Biggs H25, Harrison E26, Deen SS27, Patterson A28, Lanz T29, Kingsbury Z30, Ross M31, Basu B32, Baird R33, Lomas DJ34, Sala E35, Wason J36, Rueda OM37, Chin SF38, Wilkinson IB39, Graves MJ40, Abraham JE41, Gilbert FJ42, Caldas C43, Brindle KM44 |
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Abstract Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized C label exchange between injected [1-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 C MRSI was performed following injection of hyperpolarized [1-C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 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 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 ( = 0.903, = 0.005) and MCT 1 ( = 0.85, = 0.032) and HIF1α expression ( = 0.83, = 0.043). Imaging of hyperpolarized [1-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. |
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Copyright © 2020 the Author(s). Published by PNAS. |
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KEYWORDS: breast cancer, cancer metabolism, magnetic resonance imaging, metabolic imaging |
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Publikations ID: 31964840 Quelle: öffnen |
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