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Oxygen measurements to improve singlet oxygen dosimetry

Photodynamic therapy (PDT) involves interactions between the three main components of light fluence, photosensitizer concentration, and oxygenation. Currently, singlet oxygen explicit dosimetry (SOED) has focused on the first two of these components. The macroscopic model to calculate reacted singlet oxygen has previously involved a fixed initial ground state oxygen concentration. A phosphorescence-based oxygen probe was used to measure ground state oxygen concentration throughout treatments for mice bearing radioactively induced fibroscarcoma tumors. Photofrin-, BPD-, and HPPH-mediated PDT was performed on mice. Model-calculated oxygen and measured oxygen was compared to evaluate the macroscopic model as well as the photochemical parameters involved. Oxygen measurements at various depths were compared to calculated values. Furthermore, we explored the use of noninvasive diffuse correlation spectroscopy (DCS) to measure tumor blood flow changes in response to PDT to improve the model calculation of reacted singlet oxygen. Mice were monitored after treatment to see the effect of oxygenation on long-term recurrence-free survival as well as the efficacy of using reacted singlet oxygen as a predictive measure of outcome. Measurement of oxygenation during treatment helps to improve SOED as well as confirm the photochemical parameters involved in the macroscopic model. Use of DCS in predicting oxygenation changes was also investigated.