Interstitial photodynamic therapy and glioblastoma: Light fractionation in a preclinical model

Lasers Surg Med. 2017 Jul;49(5):506-515. doi: 10.1002/lsm.22620. Epub 2016 Dec 24.

Abstract

Background: Glioblastoma is a high-grade cerebral tumor with local recurrence and poor outcome. Photodynamic therapy (PDT) is a localized treatment based on the light activation of a photosensitizer (PS) in the presence of oxygen, which results in the formation of cytotoxic species. The delivery of fractionated light may enhance treatment efficacy by reoxygenating tissues.

Objective: To evaluate the efficiency of two light-fractionation schemes using immunohistological data.

Materials and methods: Human U87 cells were grafted into the right putamen of 39 nude rats. After PS precursor intake (5-ALA), an optic fiber was introduced into the tumor. The rats were randomly divided into three groups: without light, with light split into 2 fractions and with light split into 5 fractions. Treatment effects were assessed using brain immunohistology.

Results: Fractionated treatments induced intratumoral necrosis (P < 0.001) and peritumoral edema (P = 0.009) associated with a macrophagic infiltration (P = 0.006). The ratio of apoptotic cells was higher in the 5-fraction group than in either the sham (P = 0.024) or 2-fraction group (P = 0.01). Peripheral vascularization increased after treatment (P = 0.017), and these likely new vessels were more frequently observed in the 5-fraction group (P = 0.028).

Conclusion: Interstitial PDT with fractionated light resulted in specific tumoral lesions. The 5-fraction scheme induced more apoptosis but led to greater peripheral neovascularization. Lasers Surg. Med. 49:506-515, 2017. © 2016 Wiley Periodicals, Inc.

Keywords: 5-ALA; U87; glioblastoma; immunohistology; photodynamic therapy.

MeSH terms

  • Aminolevulinic Acid / therapeutic use*
  • Animals
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Disease Models, Animal
  • Dose Fractionation, Radiation
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Photochemotherapy*
  • Photosensitizing Agents / therapeutic use*
  • Rats
  • Rats, Nude

Substances

  • Photosensitizing Agents
  • Aminolevulinic Acid