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

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.

Authors:: R Woitek, MA McLean, S Ursprung, OM Rueda, R Manzano Garcia, MJ Locke, L Beer, G Baxter, L Rundo, E Provenzano, J Kaggie, A Patterson, A Frary, J Field-Rayner, V Papalouka, J Kane, AJV Benjamin, AB Gill, AN Priest, DY Lewis, R Russell, A Grimmer, B White, B Latimer-Bowman, I Patterson, A Schiller, B Carmo, R Slough, T Lanz, J Wason, RF Schulte, S-F Chin, MJ Graves, FJ Gilbert, JE Abraham, C Caldas, KM Brindle, E Sala, FA Gallagher

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