PDT Dose Parameters Impact Tumoricidal Durability and Cell Death Pathways in a 3D Ovarian Cancer Model

The successful implementation of photodynamic therapy (PDT)-based regimens depends on an improved understanding of the dosimetric and biological factors that govern therapeutic variability. Here, the kinetics of tumor destruction and regrowth are characterized by systematically varying benzoporphyrin derivative (BPD)-light combinations to achieve fixed PDT doses (MxJcm(-2)). Three endpoints were used to evaluate treatment response: (1) Viability evaluated every 24h for 5days post-PDT; (2) Photobleaching assessed immediately post-PDT; and (3) Caspase-3 activation determined 24h post-PDT. The specific BPD-light parameters used to construct a given PDT dose significantly impact not only acute cytotoxic efficacy, but also treatment durability. For each dose, PDT with 0.25M BPD produces the most significant and sustained reduction in normalized viability compared to 1 and 10M BPD. Percent photobleaching correlates with normalized viability for a range of PDT doses achieved within BPD concentrations. To produce a cytotoxic response with 10M BPD that is comparable to 0.25 and 1M BPD a reduction in irradiance from 150 to 0.5mWcm(-2) is required. Activated caspase-3 does not correlate with normalized viability. The parameter-dependent durability of outcomes within fixed PDT doses provides opportunities for treatment customization and improved therapeutic planning.