Evaluation of Fractionated Photofrin-mediated Photodynamic Therapy Using Different Light Fluences with Reactive Oxygen Species Explicit Dosimetry (ROSED).

Abstract

Photodynamic therapy (PDT) is an established modality for cancer treatment, and reactive oxygen species explicit dosimetry (ROSED), based on direct measurements of in-vivo light fluence (rate), in-vivo photofrin concentration, and tissue oxygenation concentration, has been proved to provide the best dosimetric quantity which can be used to predict non-fractionated PDT outcome. This study performed ROSED for Photofrin-mediated PDT for mice bearing radiation-induced fibrosacorma (RIF) tumor. As demonstrated by our previous study, fractionated PDT with a 2-hour time interval can significantly improve the long-term cure rate (from 15% to 65% at 90 days), and it tends to increase as the light dose for the first light fraction gets larger. This study focused on further improving the long-term cure rate without introducing apparent toxicity using combinations of different first light fraction lengths and total light fluences. Photofrin was injected through the mouse tail vein at a concentration of 5 mg/kg. After 18~24 hours, treatment was delivered with a collimated laser beam of 1 cm diameter at 630 nm. Mice were treated using two fractions of light fluences with a 2-hour dark interval. Different dose metrics were quantified, including light fluence, PDT dose, and [ROS]rx. In addition, the total reacted [ROS]rx and treatment outcomes were evaluated and compared to identify the optimal light fraction length and total light fluence.