Photodynamic Therapy of Disseminated Peritoneal Tumor Using New Photosensitizers

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DESCRIPTION (provided by applicant): Disseminated peritoneal cancer is caused by the spread of primary epithelial cancer as a result of shedding cells followed by implantation into other tissues and organs within the peritoneum. It occurs in late stages of cancer but is also responsible for tumor recurrence in patients with resectable tumors that lack hematogenous or lymphatic metastasis due to the presence of residual or seeded (from surgery) disease cells. Thus an adjuvant treatment for this micrometastasis, typically chemotherapy, is required. However, recurrence rates are still unacceptably high and the therapeutic outcome is often uncertain. It is proposed to develop a new adjunct therapy using photosensitizers for photodynamic therapy that have been shown in Phase I to be more efficacious than Photofrin at light induced killing of various cancer cell lines in vitro. Photodynamic therapy (PDT) is a procedure that uses a non-toxic photosensitizer (PS) and visible light to generate reactive oxygen species (ROS) that kill tumor cells. One advantage of PDT is its level of selectivity, achieved through PS that selectively target specific cell or tissue types, and the ability to control the illumination area. For intraperitoneal PDT, the peritoneum is filled with a light scattering fluid and PS. The cavity is then illuminated either immediately after surgery directly into the open cavity or with a fiber optic cable through a small incision. Because the entire cavity is treated, undetected micrometastases can be eradicated. One major advantage of our PS is that laser light is not needed. In addition, because fullerenes do not absorb red light, phototoxicity related to deep tissue penetrating light is minimized. To accomplish the goals of Phase II, we will synthesize new compounds based on established structure-activity relationships and screen them in vitro for PDT efficacy. The lead PS candidate along with the PS developed in Phase I will then be carried into in vivo studies in three mouse cancer models: ovarian, colorectal, and reticulum cell sarcoma PUBLIC HEALTH RELEVANCE: Disseminated peritoneal cancer of various forms affect thousands of Americans every year. Current adjuvant chemotherapy after surgery has traditionally been the best line of defense against disease recurrence. However, the unacceptably low 5-year survival rate necessitates the development of alternative treatments such as photodynamic therapy.