Stereotactic interstitial photodynamic therapy of recurrent malignant glioma: phase I study

• Project/Area Number: 17K10879
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Osaka Medical and Pharmaceutical University
• Principal Investigator: Kuroiwa Toshihiko 大阪医科薬科大学, その他部局等, 名誉教授 (30178115)
• Co-Investigator(Kenkyū-buntansha): 梶本 宜永 大阪医科薬科大学, 医学部, 教授 (30224413)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 悪性神経膠腫 / 光線力学療法 / 5-aminolevulinic acid / 腫瘍幹細胞 / 一重項酸素 / 光線力学治療 / 5-アミノレブリン酸 / 組織内照射 / プロトポルフィリン / プロトポルフィリンIX / ５－アミノレブリン酸 / ５アミノレブリン酸 / 光線力学診断

Outline of Final Research Achievements

Due to delays in the development of the irradiation planning system, the phase 1 clinical trial for 5-ALA PDT could not be initiated. However, basic research necessary for 5-ALA PDT continued, and we were able to demonstrate its efficacy on glioma stem cells refractory to treatment from two aspects. First, we proved its efficacy on glioma stem cells under hypoxic conditions. Second, we demonstrated its efficacy even on more treatment-resistant mesenchymal glioma stem cells. Meanwhile, a clinical simulation method for 5-ALA PDT in malignant brain tumors was developed using a singlet oxygen model and a singlet oxygen threshold for inducing cell death under light irradiation.

Academic Significance and Societal Importance of the Research Achievements

悪性神経膠腫は、免疫療法や免疫療法が進歩した現在でも難治性の悪性腫瘍である。5-ALA PDTは、低侵襲な次世代治療として期待されており、活性酸素を介しているため、その照射計画は複雑になる。本研究では、その困難さにより臨床試験には到達できなかったが、一重項酸素モデルと一重項酸素閾値を使用した悪性脳腫瘍に対する5-ALA PDTの照射シミュレーション手法を開発した。また、最も治療抵抗性が強いとされる間葉系や低酸素環境下での腫瘍幹細胞においても5-ALA PDTが有効であることを示した。これらの結果は、5-ALA PDTの臨床応用に必要な基礎的基盤を築くことができたことを示している。

Research Products

• [Journal Article] The Characteristic of Light Sources and Fluorescence in the 3-Dimensional Digital Exoscope “ORBEYE” for 5-Aminolevulinic Acid?Induced Fluorescence-Guided Surgery Compared with a Conventional Microscope (2022)
  • Author(s): Ikeda Naokado、Furuse Motomasa、Futamura Gen、Kimura Seigo、Nonoguchi Naosuke、Kawabata Shinji、Kameda Masahiro、Yokoyama Kunio、Takami Toshihiro、Kawanishi Masahiro、Kajimoto Yoshinaga、Kuroiwa Toshihiko、Wanibuchi Masahiko
  • Journal Title: World Neurosurgery Volume: 167 Pages: e1268-e1274
  • DOI: 10.1016/j.wneu.2022.09.008
  • Peer Reviewed
• [Journal Article] The effect of hypoxia on photodynamic therapy with 5-aminolevulinic acid in malignant gliomas (2022)
  • Author(s): Ihata Tomohiro、Nonoguchi Naosuke、Fujishiro Takahiro、Omura Naoki、Kawabata Shinji、Kajimoto Yoshinaga、Wanibuchi Masahiko
  • Journal Title: Photodiagnosis and Photodynamic Therapy Volume: 40 Pages: 103056-103056
  • DOI: 10.1016/j.pdpdt.2022.103056
  • Peer Reviewed
• [Journal Article] Determination of Optical Properties of Human Brain Tumor Tissues From 350 to 1000 Nm to Investigate the Cause of False Negatives in Fluorescence-Guided Resection With 5-aminolevulinic Acid (2019)
  • Author(s): Honda Norihiro, Katsunori Ishii, Yoshinaga Kajimoto, Toshihiko Kuroiwa, Kunio Awazu
  • Journal Title: J Biomed Opt. Volume: 23 Issue: 07 Pages: 1-10
  • DOI: 10.1117/1.jbo.23.7.075006
  • Peer Reviewed / Open Access