5-Aminolevulinic acid radiodynamic therapy for treatment of high-grade gliomas: A systematic review

Introduction: Radiodynamic therapy (RDT) involves administration of a radiosensitizing agent and its subsequent activation by ionizing radiation for destruction of neoplastic cells. Materials and methods: A comprehensive evaluation of the literature was performed to review the history of RDT using porphyrins for solid tumors, the cellular mechanisms of action, immunomodulatory effects, and both preclinical and clinical studies for use in high-grade gliomas (HGGs). This manuscript was prepared in accordance with the PRISMA guidelines. Results: A total of 271 articles were considered for initial review. After removal of duplicates, articles not unrelated to specific topic, and exclusion of commentary articles, a total of 11 articles were subject to full analysis that included in vivo, in vitro, and human studies. Porphyrins such as 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) selectively accumulate in neoplastic cells and are currently used for fluorescent-guided surgical resection and photodynamic therapy (PDT) of HGG and other brain tumors. 5-ALA is also shown to act as a radiosensitizer by increasing oxidative stress in neoplastic cell mitochondria and enhancing the host immune response. Postoperative radiation therapy is currently the standard of care for treatment of HGG. Conclusion: RDT remains a promising adjuvant therapy for HGGs and requires further investigation. Clinical trials of 5-ALA RDT for HGG are needed to evaluate the optimum timing, dosing and effectiveness.