Program Information
Effect of Tissue Oxygenation for Photofrin-Mediated Photodynamic Therapy
R Penjweini*, M Kim , T Zhu , University of Pennsylvania, Philadelphia, PA
Presentations
WE-RAM3-GePD-TT-1 (Wednesday, August 2, 2017) 10:30 AM - 11:00 AM Room: Therapy ePoster Theater
Purpose: Photofrin-mediated photodynamic therapy (PDT), which is based on the interactions among Photofrin, light, and oxygen, has been studied in pre-clinical and clinical trials for the treatment of some cancers and pre-cancers. PDT is categorized as type I and type II depending on the reactive oxygen species ([ROS]rx) generated to be superoxide anion (and its secondary ROSs) or singlet oxygen, respectively, for tumor toxicity. Type I interaction can also include direct triplet interaction of the photosensitizer with tissue in the presence of oxygen. Photofrin is generally considered as a type II photosensitizer but there might exist some type I photodynamic interactions. In this study we will examine whether low oxygen concentration in tumors can reduce the tumor killing by PDT.
Methods: Hypoxic and oxygenated radiation-induced fibrosarcoma (RIF) tumors were initiated by injection of 1×10⁷ cells/ml into the right mouse flank or shoulder, respectively. Photofrin at a dosage of 5 mg/kg was injected through the mouse tail vein, when the tumors had grown to a diameter of ~4-5 mm. After 24-h drug-light interval, flank and shoulder tumors were treated at a light dose of 250 J/cm², and fluence rate of 50 mW/cm². The survival curves were evaluated for each treated group as compared to the control tumors with no Photofrin and illumination.
Results: Whereas RIF tumors treated in hypoxic condition (flank tumor) did not show any significant improvement as compared to the controls, those treated with PDT in the presence of oxygen (shoulder tumors) showed 60% survival after two weeks follow up.
Conclusion: In this study we have shown that PDT efficacy reduces with decreasing tissue oxygen concentration. Thus, we conclude that there is insignificant cytotoxicity due to the direct triplet interaction (type I) and interaction due to the singlet oxygen (type II) is dominate for Photofrin-mediated PDT.
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