Abstract
Photodynamic therapy (PDT) is an effective non-ionizing treatment modality that is currently being used for various malignant and non-malignant diseases. In type II PDT with photosensitizers such as benzoporphyrin monoacid ring A (BPD), cell death is based on the creation of singlet oxygen ((1)O(2)). With a previously proposed empirical five-parameter macroscopic model, the threshold dose of singlet oxygen ([(1)O(2)](rx,sh)]) to cause tissue necrosis in tumors treated with PDT was determined along with a range of the magnitude of the relevant photochemical parameters: the photochemical oxygen consumption rate per light fluence rate and photosensitizer concentration (ξ), the probability ratio of (1)O(2) to react with ground state photosensitizer compared to a cellular target (σ), the ratio of the monomolecular decay rate of the triplet state photosensitizer (β), the low photosensitizer concentration correction factor (δ), and the macroscopic maximum oxygen supply rate (g). Mice bearing radiation-induced fibrosarcoma (RIF) tumors were treated interstitially with a linear light source at 690nm with total energy released per unit length of 22.5-135J/cm and source power per unit length of 12-150mW/cm to induce different radii of necrosis. A fitting algorithm was developed to determine the photochemical parameters by minimizing the error function involving the range between the calculated reacted singlet oxygen ([(1)O(2)](rx)) at necrosis radius and the [(1)O(2)](rx,sh). [(1)O(2)](rx) was calculated based on explicit dosimetry of the light fluence distribution, the tissue optical properties, and the BPD concentration. The initial ground state oxygen concentration ([(3)O(2)](0)) was set to be 40μM in this study. The photochemical parameters were found to be ξ=(55±40)×10(-3)cm(2)mW(-1)s(-1), σ=(1.8±3)×10(-5)μM(-1), and g=1.7±0.7μMs(-1). We have taken the literature values for δ=33μM, and β=11.9μM. [(1)O(2)](rx) has shown promise to be a more effective dosimetry quantity for predicting necrosis than either light dose or PDT dose, where the latter is simplistically a temporal integral of the products of the photosensitizer concentration and light fluence rate.