Sonodynamic Therapy for Malignant Glioma Using 220-kHz Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound and 5-Aminolevulinic acid |
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Authors: | Michiharu Yoshida Hiroyuki Kobayashi Shunsuke Terasaka Shogo Endo Shigeru Yamaguchi Hiroaki Motegi Rachmilevitch Itay Shuji Suzuki Omer Brokman Yeruham Shapira Kenji Moriyama Yumiko Kawase Toshiaki Akahane Yasutaka Kato Hajime Kamada Kiyohiro Houkin |
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Affiliation: | 2. Department of Neurosurgery, Hokuto Hospital, Obihiro, Hokkaido, Japan;3. InSightec Ltd., Tirat Carmel, Israel;4. Department of Radiology, Hokuto Hospital, Obihiro, Japan;5. Department of Biology and Genetics, Laboratory of Cancer Medical Science, Hokuto Hospital, Obihiro, Japan |
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Abstract: | Sonodynamic therapy (SDT) is used to treat various malignancies and can be applied to brain tumors using a transcranial magnetic resonance imaging-guided focused ultrasound (TcMRgFUS) device. This study investigated the efficacy of 220-kHz TcMRgFUS combined with 5-aminolevulinic acid (5-ALA) on malignant glioma in vitro and in vivo. F98 cells were irradiated with focused ultrasound (FUS) (4000 J, 20 W, 240 s, 100% duty cycle, target medium temperature <40°C) after treatment with 200 µg/mL 5-ALA, and cell viability and apoptosis were evaluated with the water-soluble tetrazolium-1 assay, triple fluorescent staining and Western blot analysis 20 h later. The anti-tumor effects of 5-ALA combined with FUS (500 J, 18 W, 30 s, 100% duty cycle, 10 repeats, target tissue temperature ≤42°C) were assessed on the basis of changes in tumor volume determined by MRI and histopathological analysis before and after treatment. The FUS/5-ALA combination reduced cell viability by inducing apoptosis and suppressed tumor proliferation and invasion as well as angiogenesis in vivo, while causing minimal damage to normal brain tissue. SDT with 220-kHz TcMRgFUS and 5-ALA can be safely used for the treatment of malignant glioma. |
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Keywords: | Sonodynamic therapy Transcranial magnetic resonance imaging-guided focused ultrasound 5-Aminolevulinic acid Malignant glioma |
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