Evaluation of singlet oxygen explicit dosimetry for predicting treatment outcomes of benzoporphyrin derivative monoacid ring A-mediated photodynamic therapy

Existing dosimetric quantities do not fully account for the dynamic interactions between the key components of photodynamic therapy (PDT) or the varying PDT oxygen consumption rates for different fluence rates. Using a macroscopic model, reacted singlet oxygen ([O21]rx) was calculated and evaluated for its effectiveness as a dosimetric metric for PDT outcome. Mice bearing radiation-induced fibrosarcoma tumors were treated with benzoporphyrin derivative monoacid ring A (BPD) at a drug-light interval of 3 h with various in-air fluences (30 to 350 J/cm2) and in-air fluence rates (50 to 150 mW/cm2). Explicit measurements of BPD concentration and tissue optical properties were performed and used to calculate [O21]rx, photobleaching ratio, and PDT dose. For four mice, in situ measurements of O23 and BPD concentration were monitored in real time and used to validate the in-vivo photochemical parameters. Changes in tumor volume following treatment were used to determine the cure index, CI=1−k/kctr, where k and kctr are the tumor regrowth rates with PDT and without PDT, respectively. The correlation between CI and the dose metrics showed that the calculated [O21]rx at 3 mm is an effective dosimetric quantity for predicting treatment outcome and a clinically relevant tumor regrowth endpoint.