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

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 ([Formula: see text]) effects, which impact the photochemical oxygen consumption rate, are not accounted for. In this preclinical study, reacted reactive oxygen species ([Formula: see text]) was investigated as a dosimetric quantity for PDT outcome. The ability of [Formula: see text] to predict the cure index (CI) of tumor growth, [Formula: see text] , where [Formula: see text] and [Formula: see text] 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 ([Formula: see text] to [Formula: see text]) and in-air fluence rates ([Formula: see text] to [Formula: see text]) with a BPD dose of [Formula: see text] 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 [Formula: see text]. Light fluence rate at 3-mm depth ([Formula: see text]), determined based on Monte-Carlo simulations, was used in the calculation of [Formula: see text] at the base of tumor. CI was used as an endpoint for three dose metrics: light fluence, PDT dose, and [Formula: see text]. PDT dose was defined as the product of the time-integral of photosensitizer concentration and [Formula: see text]. Preliminary studies show that [Formula: see text] best correlates with CI and is an effective dosimetric quantity that can predict treatment outcome. The threshold dose for [Formula: see text] 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.