Article
Influence of oxygen concentration and irradiation fractionation on Aminolevulinic Acid (ALA) guided Photodynamic Therapy (PDT) on human malignant glioma cells in vitro
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Published: | April 28, 2011 |
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Objective: Resection followed by radiation and chemotherapy are well established treatments for high-grade gliomas. However, in almost 100% of cases, the tumor recurs. Therefore innovative treatment options are required. The extent of resection, optimally guided by ALA, is important for overall outcome. Beyond that, ALA is a well examined compound for photodynamic treatment after or instead of surgery in several disciplines. In this study we examined the influence of excess oxygen supply and light fractionation on the efficacy of PDT. Light fractionation theoretically results in sensitizer replenishment during irradiation gaps in comparison to continued irradiaiton.
Methods: G112 cells were disseminated on 96-well-plates and incubated in ALA and placed in a self-developed irradiation chamber. First of all, the cells were treated by ALA (25 μg/ml cell suspension) and light (25mW/cm2) without additional oxygen and with only one single fraction of irradiation (450s). This resulted in 50% cell death as shown by colorimetric ELISA-Reader. Oxygen-treated cells were maintained in an oxygen enriched atmosphere (100%) for 15 minutes. For safety reasons oxygen supply was turned off during laser treatment. For fractionation, cells underwent irradiation treatment with 3 separate treatments with duration of 150 seconds and delays of 10 minutes.
Results: Oxygen pre-treatment resulted in significantly increased tumor cell death (up to 28%), whereas cell death was decreased in the group treated by light fractionation (up to 34%).
Conclusions: Our results demonstrate excess oxygen to improve the efficacy of photodynamic therapy while fractionation cannot improve the effect. Clinical PDT should therefore be performed with a high intraoperative fraction of inspired oxygen (FiO2).