The objective of the proposal is to provide a critical body of knowledge with the ultimate goal of transferring photodynamic therapy (PDT) to the clinical arena for the treatment of prostate cancer. The widespread use of PSA test as an adjunct to digital rectal examination has led to an increase in the diagnosis of prostate cancer in its early stages. Treatment of organ confined prostatic cancer includes radical prostatectomy, radiotherapy, brachytherapy and cryosurgical ablation. Results from all these are favorable at least in terms of short outcomes. Still, with Tic disease, 30 percent of patients will have biochemical failure within 5 years of treatment. Clearly novel methods of prostate cancer treatment are needed. We want to utilize PDT as a novel approach to the treatment of prostatic cancer. PDT for prostate cancer depends on the sequestration of a PDT drug within the glandular tissue of the prostate. The photosensitizer is subsequently activated by high-energy light producing cytotoxic substances, which in turn destroy cancerous tissue. Since prostate cancer is a multi-focal disease, PDT must ablate the prostate completely. Complete ablation will depend on quantification of tissue sensitivity to a photosensitizer, precise placement of light sources in the prostate and delivery of a therapeutic light dose to the entire gland. The prostate is irregular in shape, so transurethral light delivery cannot be used for the treatment of the majority of prostate cancers. Additionally, most cancers are located in the peripheral zone of the prostate, an area unlikely to be reached by transurethrally launched light. Sources of light and their spatial distribution must be tailored to each patient. More uniform light distribution can be achieved by interstitial light irradiation. In this case, the light is delivered by diffusers placed within the substance of the prostate parallel to the urethra at a distance optimized to deliver adequate levels of light and to create the desired photodynamic effect. To achieve uniform light distribution throughout the prostate we are developing a computer program that can determine treatment effects by calculating the distribution of light energy depending on the number of light sources placed in the prostate, their position in the gland, the dimension of the prostate, and the tissue attenuation coefficient.
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