The Efficacy of Photodynamic Therapy in Combination with Chemoradiation in Glioblastoma
Introduction: 5-ALA, recently FDA approved for GBM fluorescence-guided surgery (FGS), was studied in a rodent photodynamic therapy (PDT) model due to its preferential uptake by GBM cells and conversion to the photosensitizing metabolite, protoporphyrin IX (PpIX). In this experiment, the efficacy of 5-ALA PDT in an experimental GBM model in combination with chemoradiation (CRT) was studied.
Objective: Discuss the use of 5-ALA PDT for targeting GBM tumors due to the selective uptake of 5-ALA and production of protoporphyrin IX (PpIX).
Discuss the toxicity of 5-ALA PDT in a rodent glioma model.
Discuss the antitumor effect of 5-ALA PDT in combination with chemoradiation.
Methods: A safety study was performed in healthy mice, which underwent intracranial 5-ALA (200mg/kg IP) PDT (20J, 635nm). An efficacy study was performed on an invasive, EGFRvIII-expressing radioresistant orthotopic GBM mouse model using 5-ALA PDT, and/or fractionated CRT (5mg/kg TMZ IP; 3Gyx2 whole-brain). Tumor volume quantification was performed through serial MRI volumetric measurements, and the rodents were monitored for signs of tumor growth.
Results: Healthy mice undergoing 5-ALA PDT did not show any short- or long-term side effects. In the efficacy study, the mean tumor volume in the control group at day 14 was 154.5 ± 65.4mm3, and in the 5-ALA PDT-only group at day 21 was 114.3 ± 102.9mm3. At day 28, the mean tumor volumes for the CRT-only group and 5-ALA PDT + CRT group were 197.5 ± 82.7mm3 and 68.3 ± 86.7mm3, respectively.
Conclusions: 5-ALA PDT is a safe procedure in rodents. A marked decrease in tumor growth rate was observed after the combination of 5-ALA PDT + CRT therapy in a therapy-resistant GBM rodent model. These observations form the basis for further exploration of the efficacy of PDT combination therapy in the treatment of GBM.