Singlet oxygen explicit dosimetry to predict local tumor control for HPPH-mediated photodynamic therapy

摘要

This preclinical study examines four dosimetric quantities (light fluence, photosensitizer photobleaching ratio, PDT dose, and reacted singlet oxygen ([~1O_2]_(rx)) to predict local control rate (LCR) for 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH)-mediated photodynamic therapy (PDT). Mice bearing radiation-induced fibrosarcoma (RIF) tumors were treated with an in-air fluence of 350 J/cm~2 and in-air fluence rates (Φ_(air)) of 50 and 75 mW/cm~2 with 0.25 mg/kg HPPH and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 665 nm wavelength. A macroscopic model was used to calculate [~1O_2]_(rx) based on in vivo explicit dosimetry of the tissue oxygenation, photosensitizer concentration, and tissue optical properties. PDT dose was defined as a temporal integral of drug concentration and fluence rate (Φ) at a 3 mm tumor depth. Light fluence rate was calculated throughout the treatment volume based on Monte-Carlo simulation, diffusion theory, and measured tissue optical properties. The tumor volume of each mouse was tracked for 90 days after PDT and Kaplan-Meier analyses for LCR were performed based on a tumor volume ≤100 mm~3, for four dose metrics: fluence, HPPH photobleaching ratio, PDT dose, and [~1O_2]_(rx). The results of this study showed that [~1O_2]_(rx) is the best dosimetric quantity that can predict tumor response and correlate with LCR.