Sodium accumulation in breast cancer predicts malignancy and treatment response.
Br J Cancer
; 127(2): 337-349, 2022 07.
Article
in En
| MEDLINE
| ID: mdl-35462561
ABSTRACT
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 (23Na) 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:
23Na 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 23Na 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+]i); extracellular [Na+] ([Na+]e) 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+]i. Moreover, 23Na MRI enhances the diagnostic capability of DWI and represents a novel, non-invasive biomarker of treatment response with superior sensitivity compared to DWI alone.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sodium
/
Breast Neoplasms
Type of study:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Br J Cancer
Year:
2022
Document type:
Article
Affiliation country:
Reino Unido