James, Andrew D, Leslie, Theresa K, Kaggie, Joshua D et al. (11 more authors) (2022) Sodium accumulation in breast cancer predicts malignancy and treatment response. British journal of cancer. 337–349. ISSN 1532-1827
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022, The Author(s). Funding Information: This work was supported by Cancer Research UK (A25922), Breast Cancer Now (2015NovPhD572), BBSRC (BB/S507416/1) and an EPSRC Impact Accelerator Award. FJG, JK, GB, MAM are supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Publisher Copyright: © 2022, The Author(s). |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 16 Mar 2022 12:10 |
Last Modified: | 08 Mar 2025 00:09 |
Published Version: | https://doi.org/10.1038/s41416-022-01802-w |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/s41416-022-01802-w |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:184803 |
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Description: Sodium accumulation in breast cancer predicts malignancy and treatment response
Licence: CC-BY 2.5