Abstract
<div>Abstract<p>Hyperpolarized <sup>13</sup>C-MRI is an emerging tool for probing tissue metabolism by measuring <sup>13</sup>C-label exchange between intravenously injected hyperpolarized [1–<sup>13</sup>C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized <sup>13</sup>C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric <sup>1</sup>H-MRI and hyperpolarized <sup>13</sup>C-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 <i>MCT1</i> and lactate dehydrogenase A (<i>LDHA</i>), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of <i>LDHA</i> and the hypoxia marker <i>CAIX</i> was associated with reduced relapse-free and overall survival. Hyperpolarized <sup>13</sup>C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential.</p>Significance:<p>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.</p></div>
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