Program Information
Singlet Oxygen Threshold Dose for Long-Term Tumor Control for BPD-Mediated PDT
M Kim*, R Penjweini , T Zhu , University of Pennsylvania, Philadelphia, PA
Presentations
SU-K-FS2-16 (Sunday, July 30, 2017) 4:00 PM - 6:00 PM Room: Four Seasons 2
Purpose: Dosimetry in photodynamic therapy (PDT) is critical for the use of PDT in the treatment of malignant and nonmalignant localized diseases. Calculated reacted singlet oxygen ([¹O₂]rx) is an effective dosimetric quantity that fully accounts for the dynamic interactions between light dose, photosensitizer concentration, and tissue oxygenation. The use of [¹O₂]rx was evaluated for a clinically relevant tumor treatment endpoint.
Methods: Radiation induced fibrosarcoma (RIF) tumors were grown on the shoulders of 6-8 week old female C3H mice. Tumors were treated using BPD as the photosensitizer and a 3 hour drug-light interval. Photosensitizer concentration was measured pre- and post-PDT. Measurements of photosensitizer concentration and ground state oxygen concentration were used to perform explicit dosimetry calculations and determine the reacted singlet oxygen concentration. Use of reacted singlet oxygen concentration used evaluated as a dosimetric quantity to predict long-term survival of mice for up to 90 days. Local control rate (LCR) was used to evaluate long-term survival. LCR was defined has having no tumor re-growth for up to 90 days. Kaplan-Meier analysis for LCR was done for an endpoint of tumor volumes less than 100 mm3. Fluence, PDT dose, photosensitizer photobleaching rate, and calculated reacted singlet oxygen were used as dose metrics and compared for their predictive ability. The threshold dose to determine long term control was determined with various PDT protocols.
Results: Calculated [¹O₂]rx fully accounted for all of the mice that showed LCR for up to 90 days. Light fluence, photobleaching ratio, and PDT dose did correlate with LCR, but show subject variability. Furthermore, calculated tissue oxygenation can be used for explicit dosimetry.
Conclusion: Explicit singlet oxygen dosimetry can be used to predict tumor re-growth and long-term control for BPD-mediated PDT in a RIF tumor model. The threshold dose of [¹O₂]rx for BPD-PDT is found to be > 1.1 mM.
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