Sodium accumulation in breast cancer predicts malignancy and treatment response.

Background: Breast cancer remains a leading cause of death in women and novel imaging biomarkers are urgently required. Here, we demonstrate the diagnostic and treatment-monitoring potential of non-invasive sodium (Na) MRI in preclinical models of breast cancer.

Methods: Female Rag2 Il2rg and Balb/c mice bearing orthotopic breast tumours (MDA-MB-231, EMT6 and 4T1) underwent MRI as part of a randomised, controlled, interventional study. Tumour biology was probed using ex vivo fluorescence microscopy and electrophysiology.

Results: Na MRI revealed elevated sodium concentration ([Na]) in tumours vs non-tumour regions. Complementary proton-based diffusion-weighted imaging (DWI) linked elevated tumour [Na] to increased cellularity. Combining Na MRI and DWI measurements enabled superior classification accuracy of tumour vs non-tumour regions compared with either parameter alone. Ex vivo assessment of isolated tumour slices confirmed elevated intracellular [Na] ([Na]); extracellular [Na] ([Na]) remained unchanged. Treatment with specific inward Na conductance inhibitors (cariporide, eslicarbazepine acetate) did not affect tumour [Na]. Nonetheless, effective treatment with docetaxel reduced tumour [Na], whereas DWI measures were unchanged.

Conclusions: Orthotopic breast cancer models exhibit elevated tumour [Na] that is driven by aberrantly elevated [Na]. Moreover, Na MRI enhances the diagnostic capability of DWI and represents a novel, non-invasive biomarker of treatment response with superior sensitivity compared to DWI alone.