Reactive oxygen species explicit dosimetry to predict tumor growth for benzoporphyrin derivative-mediated vascular photodynamic therapy

摘要

Photodynamic therapy (PDT) is a well-established treatment modality for cancer and other malignant diseases; however, quantities such as light fluence and PDT dose do not fully account for all of the dynamic interactions between the key components involved. In particular, fluence rate ( ) effects, which impact the photochemical oxygen consumption rate, are not accounted for. In this preclinical study, reacted reactive oxygen species ( ) was investigated as a dosimetric quantity for PDT outcome. The ability of to predict the cure index (CI) of tumor growth, , where and are the growth rate of tumor under PDT study and the control tumor without PDT, respectively, for benzoporphyrin derivative (BPD)-mediated PDT, was examined. Mice bearing radiation-induced fibrosarcoma (RIF) tumors were treated with different in-air fluences ( to ) and in-air fluence rates ( to ) with a BPD dose of and a drug-light interval (DLI) of 15 min. Treatment was delivered with a collimated laser beam of 1-cm-diameter at 690 nm. Explicit measurements of in-air light fluence rate, tissue oxygen concentration, and BPD concentration were used to calculate for . Light fluence rate at 3-mm depth ( ), determined based on Monte-Carlo simulations, was used in the calculation of at the base of tumor. CI was used as an endpoint for three dose metrics: light fluence, PDT dose, and . PDT dose was defined as the product of the time-integral of photosensitizer concentration and . Preliminary studies show that best correlates with CI and is an effective dosimetric quantity that can predict treatment outcome. The threshold dose for for vascular BPD-mediated PDT using DLI of 15 min is determined to be 0.26 mM and is about 3.8 times smaller than the corresponding value for conventional BPD-mediated PDT using DLI of 3 h.