In vivo study of the efficacy and safety of 5-aminolevulinic radiodynamic therapy for glioblastoma fractionated radiotherapy

Junko Takahashi*, Shinsuke Nagasawa, Motomichi Doi, Masamichi Takahashi, Yoshitaka Narita, Junkoh Yamamoto, Mitsushi J. Ikemoto, Hitoshi Iwahashi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

To treat malignant glioma, standard fractionated radiotherapy (RT; 60 Gy/30 fractions over 6 weeks) was performed post-surgery in combination with temozolomide to improve overall survival. Malignant glioblastoma recurrence rate is extremely high, and most recurrent tumors originate from the excision cavity in the high-dose irradiation region. In our previous study, protoporphyrin IX physicochemically enhanced reactive oxygen species generation by ionizing radiation and combined treatment with 5-aminolevulinic acid (5-ALA) and ionizing radiation, while radiodynamic therapy (RDT) improved tumor growth suppression in vivo in a melanoma mouse model. We examined the effect of 5-ALA RDT on the standard fractionated RT protocol using U251MG-or U87MG-bearing mice. 5-ALA was orally administered at 60 or 120 mg/kg, 4 h prior to irradiation. In both models, combined treatment with 5-ALA slowed tumor progression and promoted regression compared to treatment with ionizing radiation alone. The standard fractionated RT protocol of 60 Gy in 30 fractions with oral administration of 120 and 240 mg/kg 5-ALA, the human equivalent dose of photodynamic diagnosis, revealed no significant increase in toxicity to normal skin or brain tissue compared to ionizing radiation alone. Thus, RDT is expected to enhance RT treatment of glioblastoma without severe toxicity under clinically feasible conditions.

Original languageEnglish
Article number9762
JournalInternational journal of molecular sciences
Volume22
Issue number18
DOIs
Publication statusPublished - 2021 Sep

Keywords

  • 5-aminolevulinic acid
  • ATPase inhibitory factor 1
  • Fractionated radiotherapy
  • Glioblastoma
  • Glioma
  • Protoporphyrin IX
  • Radiation therapy
  • Radiodynamic therapy
  • U251MG
  • U87MG

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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