The purpose of this proposal is to investigate and develop the potential usefulness of photodynamic therapy as an approach to the management of malignant tumors, particularly brain tumors. Malignant tumors take up and retain hematoporphyrin to a much greater extent than normal tissue. Porphyrins are powerful photodynamic agnets which sensitize cells so that they can be damaged by exposure to visible light, probably through the production of singlet oxygen. This study is based on the idea that hematoporphyrin can visible light with relative sparing of porphyrin-free normal tissues. Authentic unlabeled and C14 hematoporphyrin will be purified by chromatographic and spectroscopic techniques and used for in vitro and in vivo studies. A light source suitable for exciting hematoporphyrin in tissues will be developed by using filtered light from a xenon lamp or monochromatic light from an argon laser. Cultures of malignant cells will be used to study the kinetics of hematoporphyrin uptake and binding in tumor cells and their subcellular components, and a glioma cell culture line will be used to produce malignant tumors in experimental animals. Once the optimal conditions for combining a photosensitizing agent with light irradiation are defined, photodynamic therapy may prodive a new approach to management of several human neoplasmas resistant to existing forms of treatment.