Journal of Neuro-Oncology

, Volume 141, Issue 3, pp 595–607 | Cite as

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

  • K. Mahmoudi
  • K. L. Garvey
  • A. Bouras
  • G. Cramer
  • H. Stepp
  • J. G. Jesu Raj
  • D. Bozec
  • T. M. BuschEmail author
  • C. G. HadjipanayisEmail author
Topic Review



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.


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).


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.


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.


5-Aminolevulinic acid (5-ALA) Photodynamic therapy GBM Protoporphyrin IX (PpIX) High grade glioma Photosensitizer 



Authors TMB and GMC acknowledge NIH/NCI grants P01-CA087971 and R01-CA85831 for support during the preparation of this manuscript.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Icahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Brain Tumor Nanotechnology Laboratory, Department of Neurosurgery, Tisch Cancer InstituteIcahn School of Medicine at Mount SinaiNew YorkUSA
  3. 3.Department of NeurosurgeryMount Sinai Beth IsraelNew YorkUSA
  4. 4.Department of Radiation Oncology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  5. 5.Laser-Research Laboratory, LIFE-Center, Department of UrologyUniversity Hospital of MunichMunichGermany

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