Sonodynamic Therapy for Malignant Glioma Using 220-kHz Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound and 5-Aminolevulinic acid

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

doi:10.1016/j.ultrasmedbio.2018.10.016

Sonodynamic Therapy for Malignant Glioma Using 220-kHz Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound and 5-Aminolevulinic acid

Ultrasound Med Biol. 2019 Feb;45(2):526-538. doi: 10.1016/j.ultrasmedbio.2018.10.016. Epub 2018 Dec 4.

Authors

Michiharu Yoshida¹, Hiroyuki Kobayashi², Shunsuke Terasaka³, Shogo Endo³, Shigeru Yamaguchi³, Hiroaki Motegi³, Rachmilevitch Itay⁴, Shuji Suzuki⁴, Omer Brokman⁴, Yeruham Shapira⁴, Kenji Moriyama⁵, Yumiko Kawase⁶, Toshiaki Akahane⁶, Yasutaka Kato⁶, Hajime Kamada⁷, Kiyohiro Houkin³

Affiliations

¹ Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Department of Neurosurgery, Hokuto Hospital, Obihiro, Hokkaido, Japan.
² Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. Electronic address: hiro-ko@med.hokudai.ac.jp.
³ Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
⁴ InSightec Ltd., Tirat Carmel, Israel.
⁵ Department of Radiology, Hokuto Hospital, Obihiro, Japan.
⁶ Department of Biology and Genetics, Laboratory of Cancer Medical Science, Hokuto Hospital, Obihiro, Japan.
⁷ Department of Neurosurgery, Hokuto Hospital, Obihiro, Hokkaido, Japan.

PMID: 30522817
DOI: 10.1016/j.ultrasmedbio.2018.10.016

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.

Keywords: 5-Aminolevulinic acid; Malignant glioma; Sonodynamic therapy; Transcranial magnetic resonance imaging-guided focused ultrasound.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aminolevulinic Acid
Animals
Brain / diagnostic imaging
Brain Neoplasms / therapy*
Cell Line, Tumor
Cells, Cultured
Combined Modality Therapy / methods
Disease Models, Animal
Female
Glioma / therapy*
Levulinic Acids / therapeutic use*
Magnetic Resonance Imaging / methods*
Radiology, Interventional / methods*
Rats
Rats, Inbred F344
Ultrasonic Therapy / methods*

Substances

Levulinic Acids