Broadband microwave spiral applicator (105–125 MHz) for in vitro examinations of hyperthermia-induced tumor cell death forms – first analyses with human breast cancer cells

Abstract

Purpose

Local tumor heating with microwave applicators has been used in multimodal breast cancer therapies. This hyperthermia allows to target small regions while marginally affecting healthy tissue. However, most preclinical examinations only use simplified heating methods. Microwave applicators employed for deep heating to provide the greatest depth of penetration operate in the tens to hundreds frequency. Therefore, we aimed to adapt and test a clinically often used broadband spiral applicator (105–125 MHz) for hyperthermia with clinically wanted temperatures of 41 and 44 °C in in vitro settings with human breast cancer cell lines and with simulations.

Material and Methods

A clinically used spiral-microwave applicator (105–125 MHz) was the basis for the construction, simulation, and optimization of the in vitro HT set-up under stationary conditions. Microwave effects on tumor cell death of two human breast cancer cell lines (hormone-receptor positive MCF-7 and triple-negative MDA-MB-231) were compared with conventional heating in a contact-heating chamber. Cell death forms were analyzed by AnnexinV/Propidium iodide staining.

Results

An in vitro spiral applicator microwave-based heating system that is effective at applying heat directly to adherent breast cancer cells in cell culture flasks with medium was developed. Simulations with COMSOL proved appropriate heat delivery and an optimal energy coupling at a frequency of 111 ± 2.5 MHz. Apoptosis and necrosis induction and significantly higher cell death rates than conventional heating at both temperatures were observed, and MCF-7 showed higher death rates than MDA-MB-231 tumor cells.

Conclusions

Well-characterized in vitro heating systems are mandatory for a better understanding of the biological effects of hyperthermia in tumor therapies and to finally determine optimized clinical treatment schemes.

Keywords:

• Microwave hyperthermia
• 105–125 MHz spiral applicator
• microwave frequency
• breast cancer
• cell death forms
• multimodal tumor treatment

Acknowledgments

The present work was performed by Jannik Walter in (partial) fulfillment of the requirements for obtaining the degree “Dr. med.”. We acknowledge the support by the German Research Foundation and the Friedrich-Alexander-Universität Erlangen-Nürnberg within the funding program Open Access Publishing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

This work was funded by the Bavarian Research Foundation (MikroHyperTumImmun, AZ-1495-20; Bayerische Forschungsstiftung), by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 955625, Hyperboost, and by the Erika Giehl-Foundation of the Friedrich-Alexander-Universität Erlangen-Nürnberg.

Data availability statement

The data presented in this study are available on reasonable request from the corresponding author.