Patients with abdominal sarcomas, ovarian and gastrointestinal carcinomas have a major risk of peritoneal seeding (PS), for which results of conventional treatments are poor. We hypothesize that the combination of debulking surgery with intraperitoneal photodynamic therapy (IP PDT) will be an effective means of treating PS. IP PDT is adaptable to a wide and variable surface area, can kill multiple logs of cells and is acceptably safe to abdominal viscera. We propose to study the three major components of PDT (photosensitizer, oxygen and light), to optimize this treatment. In Project 1, we will continue our ongoing Phase II Photofrin-based clinical trial, for IP PDT in patients with recurrent PS. In addition Project 1 will investigate the efficacy and toxicity of second generation photosensitizers (SPG) in both rodent tumor systems and in large animal normal tissue models, respectively, with the aim of developing one of these compounds for future clinical trials of IP PDT. Project 2 will investigate the relationships of both tumor oxygenation and photosensitizer concentrations obtained from patient tissues to PDT response and to characteristics of tumor nodules (size, location and vascularity) by using fluorinated nitroimidazole (FN) drugs which bind and image areas of hypoxia. In Project 3, we will study both oxygen consumption and tumor vascularity during the PDT process 1 itself, by evaluating both Photofrin and other SGP in preclinical models that utilize these FN drugs in image 1: analysis studies. In Project 4, measurements of hemoglobin saturation by non-invasive techniques and quantification of light fluence will be determined directly during IP PDT. Also as part of Project 4, we will I characterize the optical properties of tissues within the peritoneum in terms of tissue scattering and absorption. Utilizing information from these investigations, we will use a SGP in a new Phase I study to optimize IP PDT as curative treatment strategy in patients with PS.
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