Perfluorocarbon Emulsions Radiosensitise Brain Tumors in Carbogen Breathing Mice With Orthotopic GL261 Gliomas

PLoS One. 2017 Sep 5;12(9):e0184250. doi: 10.1371/journal.pone.0184250. eCollection 2017.

Abstract

Background: Tumour hypoxia limits the effectiveness of radiation therapy. Delivering normobaric or hyperbaric oxygen therapy elevates pO2 in both tumour and normal brain tissue. However, pO2 levels return to baseline within 15 minutes of stopping therapy.

Aim: To investigate the effect of perfluorocarbon (PFC) emulsions on hypoxia in subcutaneous and intracranial mouse gliomas and their radiosensitising effect in orthotopic gliomas in mice breathing carbogen (95%O2 and 5%CO2).

Results: PFC emulsions completely abrogated hypoxia in both subcutaneous and intracranial GL261 models and conferred a significant survival advantage orthotopically (Mantel Cox: p = 0.048) in carbogen breathing mice injected intravenously (IV) with PFC emulsions before radiation versus mice receiving radiation alone. Carbogen alone decreased hypoxia levels substantially and conferred a smaller but not statistically significant survival advantage over and above radiation alone.

Conclusion: IV injections of PFC emulsions followed by 1h carbogen breathing, radiosensitises GL261 intracranial tumors.

MeSH terms

  • Animals
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Carbon Dioxide / pharmacology
  • Carbon Dioxide / therapeutic use*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Emulsions
  • Fluorocarbons / pharmacology
  • Fluorocarbons / therapeutic use*
  • Glioma / drug therapy*
  • Glioma / pathology
  • Mice, Inbred C57BL
  • Oxygen / pharmacology
  • Oxygen / therapeutic use*
  • Radiation-Sensitizing Agents / pharmacology
  • Radiation-Sensitizing Agents / therapeutic use*
  • Survival Analysis
  • Tumor Hypoxia / drug effects

Substances

  • Emulsions
  • Fluorocarbons
  • Radiation-Sensitizing Agents
  • Carbon Dioxide
  • carbogen
  • Oxygen