Reactive oxygen species explicit dosimetry to predict tumor growth for BPD-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 (ϕ) effects are not accounted for, which has a large effect on the oxygen consumption rate. In this preclinical study, reacted reactive oxygen species ([ROS]_rx) was investigated as a dosimetric quantity for PDT outcome. We studied the ability of [ROS]_rx to predict the cure index (CI) after PDT of murine tumors; CI = 1 - k/k_ctr, where k and k_ctr are the growth rate of PDT-treated and control(untreated) tumor, respectively. Mice bearing radiation induced fibrosarcoma (RIF) tumors were treated with BPD-mediated PDT at different in-air fluences (22.5, 40, 45, 50, 70 and 100 J/cm²) and in-air ϕ (75 and 150 mW/cm²) with a BPD dose of 1 mg/kg and a drug-light interval of 15 mins. Treatment was delivered with a collimated laser beam of 1 cm diameter at 690 nm. Explicit dosimetry of initial tissue oxygen concentration, tissue optical properties, and BPD concentration was used to calculate $$ . ϕ was calculated for the treatment volume based on Monte-Carlo simulations and measured tissue optical properties. CI was used as an endpoint for four dose metrics: light fluence, PDT dose, and [ROS]_rx. 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 best correlates with CI and is an effective dosimetric quantity that can predict treatment outcome. The threshold dose for [ROS]_rx is determined to be 0.23 mM and is about 4.3 times smaller than the corresponding value for conventional BPD-mediated PDT using DLI of 3 hrs.