Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients
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, 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
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. SIGNIFICANCE: 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.
Trial registration: ClinicalTrials.gov NCT03150576.
©2021 The Authors; Published by the American Association for Cancer Research.
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Source: PubMed