Sonodynamic Therapy Using Transcranial Focused Ultrasound for Malignant Gliomas

Abstract

Malignant glioma is the adult brain tumor with the poorest prognosis, and its median overall survival is around one year. In the treatment of this disease, the surgical removal rate has the most significant influence on the prognosis, which means that adjuvant therapy such as radiation or chemotherapy has not exerted sufficient effect. Therefore it is indispensable to develop totally different ideas and methods. Among the new attempts, photodynamic therapy (PDT) has been a unique presence. We focused on this and investigated its effect in vitro on PDT using 5-aminolevulinic acid (ALA) as a photosensitizer. In fact, in 2014, PDT was approved for glioblastoma treatment in Japan by the results of clinical trial by the Japanese research group. However, the major problems of PDT are that penetration depth of the light in brain tissue is limited and that craniotomy is necessary. To overcome issue of penetration depth, ultrasound has been expected as alternative energy source to excite the photosensitizer. Several research have shown that various photosensitizers are excited by ultrasound as well. This is so called sonodynamic therapy (SDT). Several studies have confirmed cytotoxic effect of SDT, although its mechanism has not been elucidated. Furthermore, the innovation of transcranial focused ultrasound presented the possibility to avoid craniotomy in SDT. Although there are a lot of problems to be solved, we expect that SDT can be a novel therapy. We think advantages of SDT are low toxic and minimally invasive profiles, hence sustainable treatment. If it is possible to control tumor growth by repeating SDT, we believe there is a possibility of leading to a paradigm shift of treatment of malignant gliomas.