Successful Photodynamic Therapy (PDT) treatment results in necrosis of target tissue. The tissue response clearly depends on the interplay between the treatment-dependent parameters of, light irradiation technique, light """"""""dose"""""""" to the tissue and administered dose of photosensitizer (PS), with the subject-dependent parameters of, photosensitizer uptake in the target tissue, tissue oxygenation and inherent tissue photosensitivity to the particular photosensitizer. For the purposes of understanding mechanisms of action of photosensitizers, and comparing the true photoeffectiveness of different photosensitizers in tumor and normal tissues, and thus the efficacy of PDT treatment, it is highly desirable to have a quantifiable measure of the true tissue photosensitivity, with the complexities of the particular treatment conditions factored out. The objectives of this study are therefore, to measure and modify the response of brain tumor and normal brain tissue to PDT, with the ultimate goal of improving the therapeutic efficacy for treatment of brain tumor.
The Specific Aims of this project to achieve these objectives are: 1.(a,b) To test the validity of a PDT threshold model for tumor and brain tissue necrosis, and to determine the threshold dose for PDT treatment in tumor and normal rat brain. The hypothesis to be tested is; if the number of photons absorbed by the photosensitizer per unit volume of tissue exceeds a critical (threshold) value, then necrosis will occur. This number may be different for normal and tumored brain. 2. To modify the PDT threshold values in brain by varying treatment parameters including: (a) photosensitizer (b) photoactivating light intensity (c) time interval between photosensitizer administration and photoactivation (di) site of treatment in brain. (dii) Time interval between photosensitizer administration and photoactivation for gray vs. white matter. Measurements of tissue concentration of photosensitizer, optical dose and tissue P02, and radius of tissue necrosis will be used to quantify both tumored and normal brain tissue photosensitivity to PDT.
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