Theoretical study of the influence of sensitizer photobleaching on depth of necrosis in photodynamic therapy

摘要

Abstract: In the context of PDT, photobleaching refers to the permanent degradation of the photosensitizer due to chemical modification or to the transient reduction of absorption caused by ground state depletion during pulsed irradiation. This paper consists of a theoretical study of the influence of both of these phenomena on the depth of necrosis achieved by PDT. Calculations were based on the assumptions that (1) the tissue is a homogeneous semi-infinite medium, (2) irradiation is a cw or pulsed broad external beam, (3) necrosis occurs when the number of photons absorbed by the photosensitizer per unit tissue volume exceeds a threshold. A six-flux model was used to calculate the fluence distribution and to include the effects due to temporal and spatial variations in photosensitizer concentration caused by the bleaching process. Results are presented as response surfaces showing contours of equal necrosis depth in the space defined by total delivered light fluence and initial photosensitizer concentration. Photobleaching modifies the response surface by introducing a steep 'cliff' and by partially eliminating the effects of photosensitizer self-shielding. Differences between transient and permanent photobleaching are illustrated and discussed. !17