Determination of Threshold Dose of Photodynamic Therapy to Measure Superficial Necrosis

Abstract

Photodynamic therapy (PDT) involves the photoinduction of cytotoxicity using a photosensitizer agent, a light source of the proper wavelength, and the presence of molecular oxygen. A model for tissue response to PDT based on the photodynamic threshold dose (D(th)) has been widely used. In this model cells exposed to doses below D(th) survive while at doses above the D(th) necrosis takes place. This study evaluated the light D(th) values by using two different methods of determination. One model concerns the depth of necrosis and the other the width of superficial necrosis. Using normal rat liver we investigated the depth and width of necrosis induced by PDT when a laser with a gaussian intensity profile is used. Different light doses, photosensitizers (Photogem, Photofrin, Photosan, Foscan, Photodithazine, and Radachlorin), and concentrations were employed. Each experiment was performed on five animals and the average and standard deviations were calculated. A simple depth and width of necrosis model analysis allows us to determine the threshold dose by measuring both depth and surface data. Comparison shows that both measurements provide the same value within the degree of experimental error. This work demonstrates that by knowing the extent of the superficial necrotic area of a target tissue irradiated by a gaussian light beam, it is possible to estimate the threshold dose. This technique may find application where the determination of D(th) must be done without cutting the tissue.