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Photodynamic therapy : theoretical and experimental approaches to dosimetry

Wang, Ken Kang-Hsin (1979 - ); Foster, Thomas H.
Fonte: University of Rochester Publicador: University of Rochester
Tipo: Tese de Doutorado Formato: Number of Pages:xx, 201 leaves
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Thesis (Ph. D.)--University of Rochester. Dept. of Physics and Astronomy, 2008.; Singlet oxygen (1O2) is the major cytotoxic species generated during photodynamic therapy (PDT), and 1O2 reactions with biological targets define the photodynamic dose at the most fundamental level. We have developed a theoretical model for rigorously describing the spatial and temporal dynamics of oxygen (3O2) consumption and transport and microscopic 1O2 dose deposition during PDT in vivo. Using experimentally established physiological and photophysical parameters, the mathematical model allows computation of the dynamic variation of hemoglobin-3O2 saturation within vessels, irreversible photosensitizer degradation due to photobleaching, therapy-induced blood flow decrease and the microscopic distributions of 3O2 and 1O2 dose deposition under various irradiation conditions. mTHPC, a promising photosensitizer for PDT, is approved in Europe for the palliative treatment of head and neck cancer. Using the theoretical model and informed by intratumor sensitizer concentrations and distributions, we calculated photodynamic dose depositions for mTHPC-PDT. Our results demonstrate that the 1O2 dose to the tumor volume does not track even qualitatively with long-term tumor responses. Thus...