<title>Effects of fluence rate on cytoxicity during photodynamic therapy</title>

Abstract

Production of <SUP>1</SUP>O<SUB>2</SUB> during PDT may be limited as a consequence of tissue oxygen depletion by the photodynamic process. This may in turn limit cytotoxicity during PDT. One possible way of controlling oxygen consumption during treatment is through modification of fluence rate. We have studied the impact of fluence rate on tumor oxygenation and direct PDT cytotoxicity using the RIF murine tumor and the photosensitizer Photofrin. Both fluence rates caused an acute decrease in tumor pO<SUB>2</SUB> to severely hypoxic levels. With 150 mW/cm<SUP>2</SUP> light median pO<SUB>2</SUB> remained low during prolonged exposure, while with 30 mW/cm<SUP>2</SUP> light median pO<SUB>2</SUB> values recovered to above control levels. When tumors treated with 135 J/cm<SUP>2</SUP> at each fluence rate were tested for cell survival in a clonogenic assay, 30 mW/cm<SUP>2</SUP> significantly decreased both cell clonogenicity and plating efficiency compared to light-only controls. Slight but insignificant decreases were found with 150 mW/cm<SUP>2</SUP>. During in vitro PDT the fluence rate of light delivery had no effect on cell survival. In summary, we have found that low fluence rate improves tumor oxygenation and direct cell effects during PDT.