Reactive oxygen species explicit dosimetry to predict local tumor control for Photofrin-mediated photodynamic therapy

Although photodynamic therapy (PDT) is an established modality for cancer treatment, current dosimetric quantities, such as light fluence and PDT dose, do not account for the differences in PDT oxygen consumption for different fluence rates (ϕ). A macroscopic model was adopted to calculate reactive oxygen species concentration ([ROS]_rx) to predict Photofrin-PDT outcome in mice bearing radiation-induced fibrosarcoma (RIF) tumors. Singlet oxygen is the primary cytotoxic species for ROS, which is responsible for cell death in type II PDT, although other type I ROS is included in the parameters used in our model. Using a combination of fluences (50-250 J/cm²) and ϕ (50 - 150 mW/cm²), tumor regrowth rate, k, was determined for each condition by fitting the tumor volume vs. time to V₀*exp(k*t). Treatment was delivered with a collimated laser beam of 1 cm diameter at 630 nm. Explicit dosimetry of initial tissue oxygen concentration, tissue optical properties, and Photofrin concentration was used to calculate [ROS]_rx,cal. ϕ was determined for the treatment volume based on Monte-Carlo simulations and measured tissue optical properties. Tissue oxygenation is measured using an oxylite oxygen probe to throughout the treatment to calculate the measured [ROS]_rx,mea. Cure index, CI = 1-k/k , for tumor gowth up to 14 days were determined as an endpoint using five dose metrics: light fluence, PDT dose, and [ROS]_rx,cal, and [ROS]_rx,mea. PDT dose was defined as the product of the time-integral of photosensitizer concentration and ϕ at a 3 mm tumor depth. Preliminary studies show that [ROS]_rx,mea best correlates with CI and is an effective dosimetric quantity that can predict treatment outcome.