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Supplementary Materials from Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients

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posted on 2023-04-05, 17:20 authored by Ramona Woitek, Mary A. McLean, Stephan Ursprung, Oscar M. Rueda, Raquel Manzano Garcia, Matthew J. Locke, Lucian Beer, Gabrielle Baxter, Leonardo Rundo, Elena Provenzano, Joshua Kaggie, Andrew Patterson, Amy Frary, Johanna Field-Rayner, Vasiliki Papalouka, Justine Kane, Arnold J.V. Benjamin, Andrew B. Gill, Andrew N. Priest, David Y. Lewis, Roslin Russell, Ashley Grimmer, Brian White, Beth Latimer-Bowman, Ilse Patterson, Amy Schiller, Bruno Carmo, Rhys Slough, Titus Lanz, James Wason, Rolf F. Schulte, Suet-Feung Chin, Martin J. Graves, Fiona J. Gilbert, Jean E. Abraham, Carlos Caldas, Kevin M. Brindle, Evis Sala, Ferdia A. Gallagher

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Funding

AstraZeneca and Cancer Research UK (CRUK)

Illumina & CRUK

Mark Foundation For Cancer Research (The Mark Foundation for Cancer Research)

Cancer Research UK Cambridge Centre

Cancer Research UK

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Cancer Research UK (CRUK)

CRUK Cambridge Centre, the CRUK & Engineering and Physical Sciences Research Council Cancer Imaging Centre in Cambridge and Manchester, Addenbrooke's Charitable Trust, and the NIHR Cambridge Biomedica

Austrian Science Fund (FWF)

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ARTICLE ABSTRACT

Hyperpolarized 13C-MRI is an emerging tool for probing tissue metabolism by measuring 13C-label exchange between intravenously injected hyperpolarized [1–13C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1H-MRI and hyperpolarized 13C-MRI before and 7–11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5–6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A (LDHA), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential. Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7–11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.

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