, "Macroscopic singlet oxygen modeling for dosimetry of Photofrin-mediated photodynamic therapy: an in-vivo study," J. Biomed. Opt. Abstract. Although photodynamic therapy (PDT) is an established modality for cancer treatment, current dosimetric quantities, such as light fluence and PDT dose, do not account for the differences in PDT oxygen consumption for different fluence rates (ϕ). A macroscopic model was adopted to evaluate using calculated reacted singlet oxygen concentration (½ 1 O 2 rx ) to predict Photofrin-PDT outcome in mice bearing radiationinduced fibrosarcoma tumors, as singlet oxygen is the primary cytotoxic species responsible for cell death in type II PDT. Using a combination of fluences (50, 135, 200, and 250 J∕cm 2 ) and ϕ (50, 75, and 150 mW∕cm 2 ), tumor regrowth rate, k, was determined for each condition. A tumor cure index, CI ¼ 1 − k ∕k control , was calculated based on the k between PDT-treated groups and that of the control, k control . The measured Photofrin concentration and light dose for each mouse were used to calculate PDT dose and ½ 1 O 2 rx , while mean optical properties (μ a ¼ 0.9 cm −1 , μ 0 s ¼ 8.4 cm −1 ) were used to calculate ϕ for all mice. CI was correlated to the fluence, PDT dose, and ½ 1 O 2 rx with R 2 ¼ 0.35, 0.79, and 0.93, respectively. These results suggest that ½ 1 O 2 rx serves as a better dosimetric quantity for predicting PDT outcome.

Abstract. An appropriate expression for the oxygen supply rate (Γ s ) is required for the macroscopic modeling of the complex mechanisms of photodynamic therapy (PDT). It is unrealistic to model the actual heterogeneous tumor microvascular networks coupled with the PDT processes because of the large computational requirement. In this study, a theoretical microscopic model based on uniformly distributed Krogh cylinders is used to calculate) that can replace the complex modeling of blood vasculature while maintaining a reasonable resemblance to reality; g is the maximum oxygen supply rate and ½ 3 O 2 ∕½ 3 O 2 0 is the volume-average tissue oxygen concentration normalized to its value prior to PDT. The model incorporates kinetic equations of oxygen diffusion and convection within capillaries and oxygen saturation from oxyhemoglobin. Oxygen supply to the tissue is via diffusion from the uniformly distributed blood vessels. Oxygen can also diffuse along the radius and the longitudinal axis of the cylinder within tissue. The relations of Γ s to ½ 3 O 2 ∕½ 3 O 2 0 are examined for a biologically reasonable range of the physiological parameters for the microvasculature and several light fluence rates (ϕ). The results show a linear relationship between Γ s and ½ 3 O 2 ∕½ 3 O 2 0 , independent of ϕ and photochemical parameters; the obtained g ranges from 0.4 to 1390 μM∕s.

, "Evaluation of singlet oxygen explicit dosimetry for predicting treatment outcomes of benzoporphyrin derivative monoacid ring A-mediated photodynamic therapy," J. Biomed. Opt. Abstract. 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 (½ 1 O 2 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∕cm 2 ) and in-air fluence rates (50 to 150 mW∕cm 2 ). Explicit measurements of BPD concentration and tissue optical properties were performed and used to calculate ½ 1 O 2 rx , photobleaching ratio, and PDT dose. For four mice, in situ measurements of 3 O 2 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 ¼ 1 − k∕k ctr , where k and k ctr are the tumor regrowth rates with PDT and without PDT, respectively. The correlation between CI and the dose metrics showed that the calculated ½ 1 O 2 rx at 3 mm is an effective dosimetric quantity for predicting treatment outcome and a clinically relevant tumor regrowth endpoint.

Abstract. Type II photodynamic therapy (PDT) is based on the photochemical reactions mediated through an interaction between a photosensitizer, ground-state oxygen (½ 3 O 2 ), and light excitation at an appropriate wavelength, which results in production of reactive singlet oxygen (½ 1 O 2 rx ). We use an empirical macroscopic model based on four photochemical parameters for the calculation of ½ 1 O 2 rx threshold concentration (½ 1 O 2 rx;sh ) causing tissue necrosis in tumors after PDT. For this reason, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH)-mediated PDT was performed interstitially on mice with radiation-induced fibrosarcoma (RIF) tumors. A linear light source at 665 nm with total energy released per unit length of 12 to 100 J∕cm and source power per unit length (LS) of 12 to 150 mW∕cm was used to induce different radii of necrosis. Then the amount of ½ 1 O 2 rx calculated by the macroscopic model incorporating explicit PDT dosimetry of light fluence distribution, tissue optical properties, and HPPH concentration was correlated to the necrotic radius to obtain the model parameters and ½ 1 O 2 rx;sh . We provide evidence that ½ 1 O 2 rx is a better dosimetric quantity for predicting the treatment outcome than PDT dose, which is proportional to the time integral of the products of the photosensitizer concentration and light fluence rate.

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