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

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&#x2009;<&#x2009;0.001) and peritumoral edema (P&#x2009;=&#x2009;0.009) associated with a macrophagic infiltration (P&#x2009;=&#x2009;0.006). The ratio of apoptotic cells was higher in the 5-fraction group than in either the sham (P&#x2009;=&#x2009;0.024) or 2-fraction group (P&#x2009;=&#x2009;0.01). Peripheral vascularization increased after treatment (P&#x2009;=&#x2009;0.017), and these likely new vessels were more frequently observed in the 5-fraction group (P&#x2009;=&#x2009;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. &#xa9; 2016 Wiley Periodicals, Inc.