Sodium accumulation in breast cancer predicts malignancy and treatment response

Breast cancer is the leading cause of cancer-related death in women worldwide. Development of novel noninvasive diagnostic and predictive pathophysiological biomarkers would represent a significant clinical improvement. Here, we explored the utility of non-invasive 23 Na MRI to profile tumour physiology using preclinical mouse models of breast cancer. We establish that tissue Na + concentration ([Na + ]) is elevated vs non-tumour regions across multiple different tumour models. Ex vivo SBFI fluorescence imaging corroborated that this elevation in tumour [Na + ] is due to increased intracellular [Na + ]. Effective treatment with cytotoxic chemotherapy reduced tumour tissue [Na + ], but was not detected by 1 H diffusion-weighted imaging (DWI). Moreover, combining 23 Na MRI and DWI measurements enabled superior classification accuracy of tumour vs non-tumour regions compared to either parameter alone. Quantification of breast tumour tissue [Na + ] using 23 Na MRI thus represents a novel, accurate, non-invasive diagnostic and predictive imaging biomarker.