Pancreatic cancer is increasing in frequency and is becoming the fourth most common cause of cancer death in the United States. Of the nearly 25,000 patients in whom the diagnosis will be made this year, no more than 150 can expect to survive 5 years. Combined modality therapy may extend survival to two years, but current techniques offer little prospect of making a significant impact on the survival of these unfortunate patients. At the time of diagnosis, nearly 40% of patients have disease localized to the pancreas and peripancreatic tissues. Even at the time of death, a significant portion of patients do not have widespread disease. Photodynamic therapy (PDT) capitalizes on the relatively selective retention of the photosensitizer Photofrin in malignant tissue and its activation by 630 nm (red) light to destroy that tissue. Preliminary investigations show promise for the application of PDT to the treatment of pancreatic carcinoma. Photofrin retention in the pancreatic tumor models studied is high, as is retention in the normal pancreas. Yet, when normal pancreas is then exposed to 630 nm light, only the pancreatic tumor reacts. The normal pancreas does not appear to be affected. Using two well characterized intrapancreatic tumor models, this proposal will help develop a program to address the use of PDT to treat human pancreatic carcinoma. It has the following aims:
Aim 1 :To fully characterize the pharmacokinetics of Photofrin/dihematoporphyrin ether (DHE) uptake and clearance in the normal pancreas and intra-pancreatic tumor in the rat and hamster models.
Aim 2 :To determine if differences in the nature of DHE exist in the normal pancreas when compared to other tissues which result in an absence of photo-oxidation of DHE and the lack of a PDT response.
Aim 3 :To determine the efficacy of PDT in the treatment of pancreatic carcinoma in the rat and hamster and subsequent effects on normal pancreatic tissues.
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