Hyperpolarised ¹³C-MRI using ¹³C-pyruvate in breast cancer: A review

Tumour metabolism can be imaged with a novel imaging technique termed hyperpolarised carbon-13 (¹³C)-MRI using probes, i.e., endogenously found molecules that are labeled with ¹³C. Hyperpolarisation of the ¹³C label increases the sensitivity to a level that allows dynamic imaging of the distribution and metabolism of the probes. Dynamic imaging of [1-¹³C]pyruvate metabolism is of particular biological interest in cancer because of the Warburg effect resulting in the intratumoural accumulation of [1-¹³C]pyruvate and conversion to [1-¹³C]lactate. Numerous preclinical studies in breast cancer and other tumours have shown that hyperpolarised ¹³C-pyruvate has potential for metabolic phenotyping and response assessment at earlier timepoints than the current clinical imaging techniques allow. The clinical feasibility of hyperpolarised ¹³C-MRI after the injection of pyruvate in patients with breast cancer has now been demonstrated, with increased ¹³C-label exchange between pyruvate and lactate present in higher grade tumours with associated increased expression of the monocarboxylate transporter 1 (MCT1), the transmembrane transporter mediating intracellular pyruvate uptake, and lactate dehydrogenase (LDH) as the enzyme catalysing the conversion of pyruvate to lactate. Furthermore, a study in patients with breast cancer undergoing neoadjuvant chemotherapy suggested that early changes in ¹³C-label exchange can distinguish between patients who reach pathologic complete response (pCR) and those who do not. This review summarises the current literature on preclinical and clinical research on hyperpolarised ¹³C-MRI with [1-¹³C]-pyruvate in breast cancer imaging.