Deep-tissue localization of magnetic field hyperthermia using pulse sequencing

Abstract

Objective

Deep-tissue localization of thermal doses is a long-standing challenge in magnetic field hyperthermia (MFH), and remains a limitation of the clinical application of MFH to date. Here, we show that pulse sequencing of MFH leads to a more persistent inhibition of tumor growth and less systemic impact than continuous MFH, even when delivering the same thermal dose.

Methods

We used an in vivo orthotopic murine model of pancreatic PANC-1 cancer, which was designed with a view to the forthcoming ‘NoCanTher’ clinical study, and featured MFH alongside systemic chemotherapy (SyC: gemcitabine and nab-paclitaxel). In parallel, in silico thermal modelling was implemented.

Results

Tumor volumes 27 days after the start of MFH/SyC treatment were 53% (of the initial volume) in the pulse MFH group, compared to 136% in the continuous MFH group, and 337% in the non-treated controls. Systemically, pulse MFH led to ca. 50% less core-temperature increase in the mice for a given injected dose of magnetic heating agent, and inflicted lower levels of the stress marker, as seen in the blood-borne neutrophil-to-lymphocyte ratio (1.7, compared to 3.2 for continuous MFH + SyC, and 1.2 for controls).

Conclusion

Our data provided insights into the influence of pulse sequencing on the observed biological outcomes, and validated the nature of the improved thermal dose localization, alongside significant lowering of the overall energy expenditure entailed in the treatment.

Keywords:

• Pulse magnetic hyperthermia
• temperature oscillations
• intermittent hyperthermia
• pulsatile heating
• thermoablation

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Acknowledgements

We thank Susann Burgold and Julia Göring for their excellent technical support.

Disclosure statement

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

Notes

1 The effectiveness of combining SyC (Gemcitabine in particular) with MFH had been corroborated in a previous in vitro experiment (Supplementary Figure 2).

Additional information

Funding

This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 685795 (NoCanTher), and in parts from the Graduate Academy of the Friedrich Schiller University Jena, Germany.