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.
Matthews
W
W
Thoracic Oncology Section, National Cancer Institute, Bethesda, Maryland 20892.
Cook
J
J
Mitchell
J B
JB
Perry
R R
RR
Evans
S
S
Pass
H I
HI
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D005453:Fluorescence; D017324:Hematoporphyrin Derivative; D006415:Hematoporphyrins / Q000627:therapeutic use*; D006801:Humans; D008027:Light; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D010778:Photochemotherapy; D014407:Tumor Cells, Cultured / Q000187:drug effects
D006415:Hematoporphyrins; D017324:Hematoporphyrin Derivative