Determination of the photodynamic threshold for normal rabbit brain and for intracranially implanted VX2 tumors

Abstract

The validity of a threshold model in photodynamic therapy (PDT) has been demonstrated in various normal animal tissues with porphyrin and phthalocyanine photosensitizers. This model states that, given a specific tissue and photosensitizer (PS), necrosis will result if the number of photons absorbed by the PS per unit volume of tissue exceeds a threshold value. The purpose of this study was to determine the threshold value for normal brain tissue and for intracranially implanted VX2 tumors using a rabbit model. Additionally, the dependence of the threshold value on other factors currently not included in the threshold model, such as oxygenation of the target tissue, was investigated. Calculation of the threshold requires knowledge of three parameters: (1) the radius of necrosis (for interstitial irradiation), (2) the light fluence at the necrotic boundary and (3) the photosensitizer concentration in the tissue. The animals were sensitized using Photofrin<SUP>TM</SUP> at various time-delays between injection of the sensitizer and illumination. The output from an argon laser was coupled into an optical fiber, which was implanted in the brain under stereotactic guidance. The animals were sacrificed 24 to 48 hours after PDT and the radius of necrosis was determined by serial microscopy. These data were used to calculate the photodynamic thresholds for normal brain and tumor tissue.