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

ABSTRACT: 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.

SUBMITTER: Mahmoudi K

PROVIDER: S-EPMC6538286 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Mahmoudi K K Garvey K L KL Bouras A A Cramer G G Stepp H H Jesu Raj J G JG Bozec D D Busch T M TM Hadjipanayis C G CG

Journal of neuro-oncology 20190118 3

<h4>Introduction</h4>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.<h4>Materials/methods</h4>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 (HG ...[more]

PMID: 30659522

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Project description:BackgroundPhotodynamic therapy (PDT) is widely used as a treatment for actinic keratoses (AK), with new sunlight-based regimens proposed as alternatives to lamp-based treatments. Prescribing indoor daylight activation could help address the seasonal temperature, clinical supervision, and access variability associated with outdoor treatments.ObjectiveTo compare the AK lesion clearance efficacy of indoor daylight PDT treatment (30 min of 5-aminolevulinic acid (ALA) pre-incubation, followed by 2 h of indoor sunlight) versus a lamp-based PDT treatment (30 min of ALA preincubation, followed by 10 min of red light).MethodsA prospective clinical trial was conducted with 41 patients. Topical 10% ALA was applied to the entire treatment site (face, forehead, scalp). Patients were assigned to either the lamp-based or indoor daylight treatment. Actinic keratosis lesion counts were determined by clinical examination and recorded for pre-treatment, 1-month, and 6-month follow-up visits.ResultsThere was no statistical difference in the efficacy of AK lesion clearance between the red-lamp (1-month clearance = 57 ± 17%, 6-month clearance = 57 ± 20%) and indoor daylight treatment (1-month clearance = 61 ± 19%, 6-month clearance = 67 ± 20%). A 95% confidence interval of the difference of the means was measured between -4.4% and 13.4% for 1-month, and -2.2% and +23.6% for 6-month timepoints when comparing the indoor daylight to the red-lamp treatment, with a priori interval of equivalence of ±20%.LimitationsEnsuring an equivalent dose between the indoor and lamp treatment cohorts limited randomisation since it required performing indoor daylight treatments only during sunny days.ConclusionIndoor-daylight PDT provided equivalent AK treatment efficacy to a lamp-based regimen while overcoming temperature limitations and UV-block sunscreen issues associated with outdoor sunlight treatments in the winter.Clinical trial registrationClinicaltrials.gov listing: NCT03805737.

Project description:Background5-Aminolevulinic acid (5-ALA), a fluorescent contrast agent, has been used for tumor paint and photodynamic therapy (PDT) for various tumors, but its use with soft tissue sarcomas is not well documented. Myxofibrosarcoma, a subtype of soft tissue sarcoma with a high local recurrence rate, may benefit from similar types of treatment. The purpose of this study was to analyze the effects of 5-ALA tumor paint and PDT on a myxofibrosarcoma cell line.MethodsTumor paint was assessed by exposing micromass pellets of human adipose-derived stromal (ADS) cells or myxofibrosarcoma (MUG-Myx1) cells to 5-ALA. Cell pellets were then visualized using a microscope at established excitation and emission wavelengths. Corrected total cell fluorescence was calculated per accepted protocols. Photodynamic therapy was similarly assessed by exposing ADS and MUG-Myx1 cells to 5-ALA, with subsequent analysis via flow cytometry and real-time confocal microscopy.ResultsThe use of 5-ALA tumor paint led to a selective fluorescence in MUG-Myx1 cells. Findings were confirmed by flow cytometry. Interestingly, flow cytometry results showed progressive selective cell death with increasing 5-ALA exposure as a result of the PDT effect. PDT was further confirmed using confocal microscopy, which revealed progressive cellular bubble formation consistent with advancing stages of cell death-a finding that was not seen in control ADS cells.Conclusions5-ALA tumor paint and PDT were successfully used on a human myxofibrosarcoma cell line (MUG-Myx1). Results from this study showed both selective fluorescent tagging and selective cytotoxicity of 5-ALA toward malignant myxofibrosarcoma cells, while sparing benign adipose control cells. This finding was further confirmed in a dramatic time-lapse video, visually confirming active, targeted cell death. 5-ALA's two-pronged application of selective tumor identification and cytotoxicity may transform surgical and medical approaches for treating soft tissue sarcomas.

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

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

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