Abstract
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.
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 language | English |
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| Pages | 533 |
| Number of pages | 1 |
| DOIs | |
| Publication status | Published - 6 Feb 2020 |
| Event | UK Interdisciplinary Breast Cancer Symposium - ICC, Birmingham, United Kingdom Duration: 27 Jan 2020 → 28 Jan 2020 |
Conference
| Conference | UK Interdisciplinary Breast Cancer Symposium |
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| Abbreviated title | UKIBCS |
| Country/Territory | United Kingdom |
| City | Birmingham |
| Period | 27/01/20 → 28/01/20 |