Assessment of breast tumour [Na+] using 23Na magnetic resonance imaging: a potential diagnostic biomarker for malignant disease

Andrew James, Joshua D. Kaggie, Frank Riemer, Gabrielle Baxter, Mary McLean, Theresa Leslie, Michaela Nelson, Ferdia A. Gallagher, Fiona J. Gilbert, Aneurin James Kennerley, Will Brackenbury

Research output: Contribution to conferenceAbstractpeer-review


Introduction: Despite advances in early stage disease treatment, metastatic breast cancer has poor prognosis. Evidence indicates that malignant tumours exhibit elevated [Na+]. Moreover, evidence sug- gests that this [Na+] elevation reduces following response to neoadjuvant chemotherapy. Numerous studies implicate an altered ionic microenvironment in tumour progression. Indeed, triple-nega- tive breast cancer cells (MDA-MB-231) aberrantly express voltage- gated sodium channels (VGSCs); these facilitate an inward Na+ current, leading to elevated intracellular [Na+] ([Na+]i) and increased invasiveness.
Aims/Objectives: Using 23Na magnetic resonance imaging approa- ches, we assessed the utility of tumour [Na+] as a novel diagnostic indicator for malignant disease.
Methods: We developed a bespoke radiofrequency coil for a 7T preclinical magnetic resonance imaging (MRI) system and measured tumour [Na+] in a xenograft mouse model of triple-negative breast cancer. Endpoint tumour [Na+] was confirmed using inductively coupled plasma mass spectrometry (ICP-MS). Na+ conductance within live tumour slices was assessed using the whole-cell patch clamp method. To measure tumour [Na+] in patients with breast cancer, a protocol was developed for a clinical 3T MRI system (MR750, GE Healthcare) using a 4-channel 23Na/16-channel 1H coil. Results: 23Na imaging and ICP-MS revealed elevated [Na+] in xenograft tumours compared with healthy mammary tissue. Standard chemotherapy (docetaxel, 10 mg/kg i.p. weekly) inhibited tumour growth rate and decreased tumour [Na+] compared with control. However, docetaxel had no effect on Na+ conductance within live tumour slices. The antiepileptic medication eslicarbazepine acetate (VGSC blocker, 200 mg/kg p.o. daily) had no effect on tumour growth, tumour [Na+], or Na+ conductance. Our clinical imaging approach was validated on healthy volunteers and recruitment for the clinical study has begun.
Conclusions: Elevated tumour [Na+] in breast cancer may represent a potential imaging biomarker for malignancy and response to chemotherapy. Moreover, targeting of elevated tumour [Na+] should be investigated as a potential treatment avenue.
Original languageEnglish
Number of pages1
Publication statusPublished - 6 Feb 2020
EventUK Interdisciplinary Breast Cancer Symposium - ICC, Birmingham, United Kingdom
Duration: 27 Jan 202028 Jan 2020


ConferenceUK Interdisciplinary Breast Cancer Symposium
Abbreviated titleUKIBCS
Country/TerritoryUnited Kingdom

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