Singlet oxygen explicit dosimetry to predict long-term local tumor control for Photofrin-mediated photodynamic therapy

摘要

Although photodynamic therapy (PDT) is an established modality for the treatment of cancer, current dosimetric quantities do not account for the variations in PDT oxygen consumption for different fluence rates (Φ). In this study we examine the efficacy of reacted singlet oxygen concentration ([~1O_2]_(rx) to predict long-term local control rate (LCR) for Photofrin-mediated PDT. Radiation-induced fibrosarcoma (RIF) tumors in the right shoulders of female C3H mice are treated with different in-air fluences of 225-540 J/cm~2 and in-air fluence rate (Φ_(air)) of 50 and 75 mW/cm~2 at 5 mg/kg Photofrin and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 630 nm wavelength. [~1O_2]_(rx) is calculated by using a macroscopic model based on explicit dosimetry of Photofrin concentration, tissue optical properties, tissue oxygenation and blood flow changes during PDT. The tumor volume of each mouse is tracked for 90 days after PDT and Kaplan-Meier analyses for LCR are performed based on a tumor volume ≤100 mm~3, for the four dose metrics light fluence, photosensitizer photobleaching rate, PDT dose and [~1O_2]_(rx). PDT dose is defined as a temporal integral of photosensitizer concentration and Φ at a 3 mm tumor depth. Φ is calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. Our preliminary studies show that [~1O_2]_(rx) is the best dosimetric quantity that can predict tumor response and correlate with LCR. Moreover, [~1O_2]_(rx) calculated using the blood flow changes was in agreement with [~1O_2]_(rx) calculated based on the actual tissue oxygenation.