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Sonodynamic therapy for gliomas

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Abstract

Introduction

Glioma remains incurable and a life limiting disease with an urgent need for effective therapies. Sonodynamic therapy (SDT) involves systemic delivery of non-toxic chemical agents (sonosensitizers) that accumulate in tumor cells or environment and are subsequently activated by exposure to low-frequency ultrasound to become cytotoxic agents. Herein, we discuss proposed mechanisms of action of SDT and provide recommendation for future research and clinical applications of SDT for gliomas.

Methods

Review of literature of SDT in glioma cell cultures and animal models published in Pubmed/MEDLINE before January, 2021.

Results

Different porphyrin and xanthene derivatives have proven to be effective sonosensitizers. Generation of reactive oxygen species and free radicals from water pyrolysis or sonosensitizers, or physical destabilization of cell membrane, have been identified as mechanisms of SDT leading to cell death. Numerous studies across glioma cell lines using various sonosensitizers and ultrasound parameters have documented tumoricidal effects of SDT. Studies in small animal glioma xenograft models have also consistently documented that SDT is associated with improved tumor control and longer survival of animals treated with SDT while avoiding damage of surrounding brain. There are no clinical trials completed to date regarding safety and efficacy of SDT in patients harboring gliomas, but some are beginning.

Conclusions

Pre-clinical studies cell cultures and animal models indicate that SDT is a promising treatment approach for gliomas. Further studies should define optimal sonication parameters and sonosensitizers for gliomas. Clinical trials of SDT in patients harboring gliomas and other malignant brain tumors are currently underway.

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Acknowledgements

The authors thank Jackie Brenner for her help in the design and for the drawing of Fig. 1.

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Authors and Affiliations

  1. Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA

    Adomas Bunevicius, Stylianos Pikis, Francesco Prada & Jason Sheehan

  2. Focused Ultrasound Foundation, Charlottesville, VA, USA

    Frederic Padilla & Francesco Prada

  3. Department of Radiology, University of Virginia, Charlottesville, VA, USA

    Frederic Padilla

  4. Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico C. Besta, Milan, Italy

    Francesco Prada

  5. University of Virginia Health System, Box 800212, Charlottesville, VA, 22908, USA

    Jason Sheehan

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  1. Adomas Bunevicius
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Correspondence to Jason Sheehan.

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Bunevicius, A., Pikis, S., Padilla, F. et al. Sonodynamic therapy for gliomas. J Neurooncol 156, 1–10 (2022). https://doi.org/10.1007/s11060-021-03807-6

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