5-aminolevulinic acid photodynamic therapy for the treatment of high-grade gliomas

• Published in: Journal of neuro-oncology Vol. 141; no. 3; pp. 595 - 607
• Main Authors: Mahmoudi, K., Garvey, K. L., Bouras, A., Cramer, G., Stepp, H., Jesu Raj, J. G., Bozec, D., Busch, T. M., Hadjipanayis, C. G.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2019; Springer Nature B.V
• Subjects: Aminolevulinic acid; Aminolevulinic Acid - therapeutic use; Animals; Brain cancer; Brain Neoplasms - complications; Brain Neoplasms - drug therapy; Brain tumors; Clinical trials; Clinical Trials as Topic; Esophagus; FDA approval; Glioma; Glioma - complications; Glioma - drug therapy; Heme; Humans; Immunomodulation; Keratosis; Literature reviews; Medicine; Medicine & Public Health; Neuroimaging; Neurology; Oncology; Photochemotherapy; Photodynamic therapy; Photosensitization; Photosensitizing Agents - therapeutic use; Surgery; Topic Review; Treatment Outcome; Tumor cells; Vascularization; 5-Aminolevulinic acid (5-ALA); Photodynamic therapy; GBM; Photosensitizer; High grade glioma; Protoporphyrin IX (PpIX)
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-019-03103-4

Introduction Photodynamic therapy (PDT) is a two-step treatment involving the administration of a photosensitive agent followed by its activation at a specific light wavelength for targeting of tumor cells. Materials/Methods A comprehensive review of the literature was performed to analyze the indications for PDT, mechanisms of action, use of different photosensitizers, the immunomodulatory effects of PDT, and both preclinical and clinical studies for use in high-grade gliomas (HGGs). Results PDT has been approved by the United States Food and Drug Administration (FDA) for the treatment of premalignant and malignant diseases, such as actinic keratoses, Barrett’s esophagus, esophageal cancers, and endobronchial non-small cell lung cancers, as well as for the treatment of choroidal neovascularization. In neuro-oncology, clinical trials are currently underway to demonstrate PDT efficacy against a number of malignancies that include HGGs and other brain tumors. Both photosensitizers and photosensitizing precursors have been used for PDT. 5-aminolevulinic acid (5-ALA), an intermediate in the heme synthesis pathway, is a photosensitizing precursor with FDA approval for PDT of actinic keratosis and as an intraoperative imaging agent for fluorescence-guided visualization of malignant tissue during glioma surgery. New trials are underway to utilize 5-ALA as a therapeutic agent for PDT of the intraoperative resection cavity and interstitial PDT for inoperable HGGs. Conclusion PDT remains a promising therapeutic approach that requires further study in HGGs. Use of 5-ALA PDT permits selective tumor targeting due to the intracellular metabolism of 5-ALA. The immunomodulatory effects of PDT further strengthen its use for treatment of HGGs and requires a better understanding. The combination of PDT with adjuvant therapies for HGGs will need to be studied in randomized, controlled studies.