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.

[1]  T. Puck,et al.  A RAPID METHOD FOR VIABLE CELL TITRATION AND CLONE PRODUCTION WITH HELA CELLS IN TISSUE CULTURE: THE USE OF X-IRRADIATED CELLS TO SUPPLY CONDITIONING FACTORS. , 1955, Proceedings of the National Academy of Sciences of the United States of America.

[2]  J Moan,et al.  PHOTOBLEACHING OF PORPHYRINS USED IN PHOTODYNAMIC THERAPY AND IMPLICATIONS FOR THERAPY , 1987, Photochemistry and photobiology.

[3]  I Rosenthal,et al.  Effect of light fluence rate on mammalian cells photosensitization by chloroaluminium phthalocyanine tetrasulphonate. , 1987, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[4]  J. Moan,et al.  Photodynamic inactivation of cancer cells in vitro. Effect of irradiation temperature and dose fractionation. , 1979, Cancer letters.

[5]  H. Pass,et al.  In vitro photodynamic therapy of human lung cancer. , 1989, The Journal of surgical research.

[6]  J. Moan,et al.  Porphyrin-sensitized photoinactivation of cells in vitro. , 1984, Progress in clinical and biological research.

[7]  M. M. ELKIND,et al.  X-Ray Damage and Recovery in Mammalian Cells in Culture , 1959, Nature.

[8]  J. Bedford,et al.  Dose-rate effects in mammalian cells in culture III. Comparison of cell killing and cell proliferation during continuous irradiation for six different cell lines. , 1979, Radiation research.

[9]  C J Gomer,et al.  Differential cell photosensitivity following porphyrin photodynamic therapy. , 1988, Cancer research.

[10]  C. Gomer,et al.  In vitro and in vivo light dose rate effects related to hematoporphyrin derivative photodynamic therapy. , 1985, Cancer research.

[11]  D. Bellnier,et al.  Photosensitization and split-dose recovery in cultured human urinary bladder carcinoma cells containing nonexchangeable hematoporphyrin derivative. , 1985, Cancer research.