In vitro photodynamic therapy of human lung cancer: investigation of dose-rate effects.

The influence of light dose-rate delivery was studied in human lung adenocarcinoma A549 cells treated with hematoporphyrin derivative (Photofrin II)-based photodynamic therapy. Clonogenic cell survival curves were generated for cells treated for 2 h with 25 micrograms/ml of Photofrin II followed by exposure to light delivered at 0.3, 0.15, 0.075, or 0.0375 milliwatts/cm2. Cellular sensitizer levels, as determined by fluorescence measurements, remained constant over the entire time course of all light exposures. As the dose rate of light delivery was decreased, a significant increase in cell survival was observed at equal light energies (225 mJ/cm2). The enhancement in survival from the highest to the lowest dose rate used was 1.6-fold (at the 50% survival level). These findings may have important clinical implications relating to photodynamic therapy of tumors and may provide a partial explanation for treatment failure.