Journal
CANCER RESEARCH
Volume 81, Issue 23, Pages -Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-21-1499
Keywords
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Categories
Funding
- Mark Foundation for Cancer Research [C9685/A25177]
- Cancer Research UK Cambridge Centre [C9685/A25177]
- Cancer Research UK (CRUK) [C8742/A18097, C19212/A16628, C19212/A27150, C197/A16465, CRUK/14/048]
- Austrian Science Fund [J4025-B26]
- CRUK Cambridge Center
- Engineering and Physical Sciences Research Council Cancer Imaging Center in Cambridge
- Manchester, Addenbrooke's Charitable Trust
- NIHR Cambridge Biomedical Research Center [BRC-1215-20014]
- National Institute for Health Research (NIHR)
- UKRI Medical Research Council [MC UU 00002/16]
- Cambridge Experimental Cancer Medicine Center
- Wellcome Trust [095962]
- Cambridge University Hospitals National Health Service Foundation Trust
- Cambridge Breast Cancer Research Unit Laboratory
- AstraZeneca [ESR-14-10241]
- CRUK Cambridge Center [C507/A27657]
- Illumina [C507/A27657]
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Hyperpolarized C-13-MRI is a promising tool for monitoring early treatment response in breast cancer, where an increase in the lactate-to-pyruvate ratio can predict pathological complete response. Overexpression of LDHA and CAIX is associated with reduced relapse-free and overall survival in breast cancer patients.
Hyperpolarized C-13-MRI is an emerging tool for probing tissue metabolism by measuring C-13-label exchange between intravenously injected hyperpolarized [1-C-13]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyper polarized C-13-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric H-1-MRI and hyperpolarized C-13-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 C-13-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. [GRAPHICS] .
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