1. Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients
- Author
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Suet-Feung Chin, Bruno Carmo, Jean Abraham, Andrew J. Patterson, Brian H. White, Amy Schiller, Ashley Grimmer, Kevin M. Brindle, Raquel Manzano Garcia, Andrew B. Gill, Joshua D. Kaggie, Rhys Slough, Gabrielle C Baxter, David Y. Lewis, Rolf F. Schulte, Arnold J. V. Benjamin, Johanna Field-Rayner, Justine Kane, Carlos Caldas, Elena Provenzano, Mary A. McLean, Matthew Locke, Ferdia A. Gallagher, Titus Lanz, Stephan Ursprung, Vasiliki Papalouka, Roslin Russell, Fiona J. Gilbert, Ramona Woitek, Lucian Beer, Martin J. Graves, Oscar M. Rueda, Ilse Patterson, Beth Latimer-Bowman, James Wason, Leonardo Rundo, Evis Sala, Andrew N. Priest, Amy Frary, McLean, Mary A [0000-0002-3752-0179], Rueda, Oscar M [0000-0003-0008-4884], Beer, Lucian [0000-0003-4388-7580], Rundo, Leonardo [0000-0003-3341-5483], Frary, Amy [0000-0002-4373-3517], Benjamin, Arnold JV [0000-0003-2063-8258], Gill, Andrew B [0000-0002-9287-9563], Priest, Andrew N [0000-0002-9771-4290], Lewis, David Y [0000-0001-9329-1326], Grimmer, Ashley [0000-0001-6013-5271], Wason, James [0000-0002-4691-126X], Gilbert, Fiona J [0000-0002-0124-9962], Brindle, Kevin M [0000-0003-3883-6287], Gallagher, Ferdia A [0000-0003-4784-5230], and Apollo - University of Cambridge Repository
- Subjects
neoadjuvant treatment ,Cancer Research ,Lactate dehydrogenase A ,medicine.medical_treatment ,Endogeny ,Hyperpolarized carbon-13 MRI ,Breast Neoplasms ,Article ,Breast cancer ,Gene expression ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,hyperpolarized magnetic resonance imaging ,education ,Neoadjuvant therapy ,education.field_of_study ,Chemotherapy ,Carbon Isotopes ,metabolic imaging ,business.industry ,Hypoxia (medical) ,medicine.disease ,Prognosis ,molecular imaging ,Magnetic Resonance Imaging ,Neoadjuvant Therapy ,Survival Rate ,Neoplasm Recurrence ,Local ,Oncology ,Cancer research ,Female ,Follow-Up Studies ,Neoplasm Recurrence, Local ,medicine.symptom ,business ,neoadjuvant chemotherapy - 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.
- Published
- 2021