Photodynamic Therapy Dosimetry Through Measurement of Fluorescence Decrease Due to Photobleaching

Abstract

The phenomenon of photobleaching of a photosensitizer during photodynamic therapy (PDT) is well known. For second generation photosensitizers it may be possible to exploit this effect to enhance the volume of damaged tissue and improve the efficacy of PDT. In addition, as a consequence of photobleaching, the fluorescence emitted by the photosensitizer will decrease during PDT. Mathematical models were developed which describe fluorescence emission, photobleaching and tissue necrosis resulting from the irradiation of tissue containing photosensitizer using an appropriate light source. Diffusion theory was used to model bleaching in a semi-infinite medium caused by broad-beam irradiation, and both pencil and broad-beam fluorescence excitation of the photosensitizer. In addition, models were developed for an isotropic point source imbedded in an infinite medium. Based on the relationship between the decreasing fluorescence signal and the increasing volume of tissue damage, these models allow the extent of necrosis achieved during treatment to be monitored. By analysing spatially resolved fluorescence measurements predictions about necrosis depth that are insensitive to treatment parameters such as photosensitizer concentration, tissue optical properties and bleach rate are possible. Tissue simulating optical phantoms that allow for relatively simple and accurate alteration to optical properties were developed. Photosensitizers which still undergo fluorescence and photobleaching in the solid medium were also added. Using these phantoms, treatment was simulated and spatially resolved fluorescence was measured as a function of time for a wide range of initial treatment parameters. Photobleaching of the photosensitizers was observed to occur through a decrease in fluorescence emission. Also, spatially resolved measurements provided information about the average photosensitizer depth, which was seen to increase with time, with little knowledge of initial treatment parameters. These experimental results were then compared with predictions from the mathematical theory, illustrating the validity of the models. The value and feasibility of this technique for photodynamic therapy dosimetry are discussed, along with planned improvements.