Effect of irradiation fluence rate on the efficacy of photodynamic therapy and tumor oxygenation in meta-tetra (hydroxyphenyl) chlorin (mTHPC)-sensitized HT29 xenografts in nude mice.

Abstract

We present direct experimental evidence of the fluence-rate-dependent, radiation-induced variations in intratumor oxygen partial pressure (pO(2)) in HT29 human colon adenocarcinoma xenografts subjected to meta-tetra(hydroxyphenyl)chlorin (mTHPC)-based photodynamic therapy (PDT). The data establish a correlation between tumor oxygenation and treatment outcome. Tumor-bearing mice were injected with 0.3 mg/kg photosensitizer and subjected 72 h later to a 12 J/cm(2) red light dose administered at fluence rates of 5, 30, 90 and 160 mW/cm(2). A significant decrease in mean and median pO(2) was registered at approximately half of the total radiation fluence was delivered in tumors treated at rates of 160 and 90 mW/cm(2). Conversely, with the two lower fluence rates, intratumor pO(2) was maintained at levels comparable to those measured before illumination. Tumor oxygenation values registered shortly after every treatment protocol were at least equal to baseline levels, thus excluding the possibility of significant acute vessel damage during illumination. The tumor regrowth profile correlated with the pO(2) values monitored during irradiation. Tumors treated with fluence rates of 5 and 30 mW/cm(2) exhibited significantly longer tumor quadrupling times than those treated at 160 and 90 mW/cm(2). Improved tumor destruction could be expected by reducing the rate and the extent of oxygen depletion during meta-tetra(hydroxyphenyl)chlorin photodynamic therapy using low fluence rates.