Hematoporphyrin derivative (HpD) photoradiation therapy (PRT) is the treatment of solid tumors by a protocol that consists of the intravenous administration of hematoporphyrin derivative followed 2 or 3 days later by a localized exposure of the tumor to red light. The preferential retention of hematoporphyrin derivative in malignant tissue compared to adjacent normal tissue, and the generation of cytotoxic oxygen species by porphyrins when illuminated with visible light account for the effectiveness of photoradiation therapy. Initial results on the clinical use of photoradiation therapy for the treatment of various types of solid tumors have been encouraging. However, there still remains a significant lack of information pertaining to many of the cellular and tissue kinetics related to porphyrin induced photodynamic action. In addition, there has been only minimal preclinical evaluation of the treatment parameters utilized in clinical photoradiation therapy. The research described in this proposal is designed to examine treatment parameters as well as study basic mechanisms related to porphyrin photoradiation therapy. Both HpD and the active component of HpD (Photofrin II) are used clinically and, therefore, both drugs will be investigated in this proposal. In-vivo procedures will be utilized to examine the parameters of wavelength of delivered light and dose rate of delivered light as they relate to photoradiation induced tumor response. Determination of the effect of general and local anesthesia on the efficiency of porphyrin photoradiation therapy will also be performed. Quantitative studies will also be performed to determine the effect of vasoactive agents on porphyrin uptake in tumor tissue. In-vivo procedures will be utilized to document the oncogenic potential of PRT, examine possible repair properties of porphyrin photoradiation and compare the sensitivity of normal and DNA repair deficient human fibroblasts exposed to porphyrin photosensitization. In addition, studies will be performed to compare the porphyrin uptake kinetics and photosensitization properties of bovine endothelial and smooth muscle cells. These studies should enhance the understanding and efficacy of photoradiation therapy.
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