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

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.