The broad, long-term objective of this proposal is to optimize intraperitoneal photodynamic therapy. To that end, we will investigate hypoxia, photosensitizer concentration, and microvascular density in human intraperitoneal tumors.
The specific aims are to (1a) examine the level of hypoxia and the inter- and intra-patient variability of hypoxia in the tumor nodules from patients with intraperitoneal malignancies, (1b) to examine the mean levels and inter- and intra-patient variability of photosensitizer in tumor nodules and normal tissues and to examine the photosensitizer concentration in tumor nodules compared to relevant normal tissues, (2) describe the quantitative relationships among photosensitizer concentration, levels of hypoxia, and microvascular density in tumor nodules, and (3) examine the association between tumor nodule hypoxia or photosensitizer concentration and clinical outcome after intraperitoneal PDT. The research design is a clinical trial in which the hypoxic marker, EF5, is administered approximately 48 hours prior to intraperitoneal photodynamic therapy. At the time of laparotomy, a minimum of 10 small tumor nodules (< 1 cm thickness) and normal tissues, as clinically indicated, will be removed. Each tumor nodule will be analyzed for EF5 binding, photosensitizer concentration, and microvascular density. EF5 binding will be measured using immunohistochemical techniques. Photosensitizer concentration will be measured using high performance liquid chromatography (HPLC). PECAMKD31 staining will be used to identify vessels in order to establish microvascular density. Statistical methods will be used to determine the adjusted and unadjusted associations between EF5 binding, photosensitizer concentration, and clinical outcome.
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