Fractionated Photofrin-Mediated Photodynamic Therapy Significantly Improves Long-Term Survival.

Simple Summary: We have demonstrated that a fractionated PDT scheme, delivered using a two-hour interval between two light delivery treatments, significantly improves long-term efficacy of Photofrin-mediated PDT while reducing side effects. Reactive Oxygen Species Explicit Dosimetry (ROSED), utilizing direct measurements of in vivo light fluence, in vivo Photofrin concentration, and in vivo tissue oxygenation concentration, were used to determine the concentration of reacted reactive oxygen species, [ROS]rx, as a dosimetry quantity for PDT treatment. We found that a threshold Photofrin dose of 0.78 mM is required for the complete cure (90-day survival) of RIF tumors using fractionated Photofrin-mediated PDT treatment. To our knowledge, this is the first report of this parameter. This study investigates the effect of fractionated (two-part) PDT on the long-term local control rate (LCR) using the concentration of reactive oxygen species ([ROS]rx) as a dosimetry quantity. Groups with different fractionation schemes are examined, including a 2 h interval between light delivery sessions to cumulative fluences of 135, 180, and 225 J/cm2. While the total treatment time remains constant within each group, the division of treatment time between the first and second fractionations are explored to assess the impact on long-term survival at 90 days. In all preclinical studies, Photofrin is intravenously administered to mice at a concentration of 5 mg/kg, with an incubation period between 18 and 24 h before the first light delivery session. Fluence rate is fixed at 75 mW/cm2. Treatment ensues via a collimated laser beam, 1 cm in diameter, emitting light at 630 nm. Dosimetric quantities are assessed for all groups along with long-term (90 days) treatment outcomes. This study demonstrated a significant improvement in long-term survival after fractionated treatment schemes compared to single-fraction treatment, with the optimal 90-day survival increasing to 63%, 86%, and 100% vs. 20%, 25%, and 50%, respectively, for the three cumulative fluences. The threshold [ROS]rx for the optimal scheme of fractionated Photofrin-mediated PDT, set at 0.78 mM, is significantly lower than that for the single-fraction PDT, at 1.08 mM. [ABSTRACT FROM AUTHOR]