MODE OF ACTION OF THE PHOTO-ACTIVATED PORPHYRINS

HPD是一种复杂的卟啉混合物，由血卟啉衍生而来

HPD, a complex mixture of porphyrins derived from hematoporphyrin, is useful in localization and therapy of solid tumors. Localization results from selective retention of component(s) of HPD by neoplastic, but not adjoining normal tissues, during the 48 hr after drug administration. Clinical usefulness of HPD is based on [1] localization of tumors at remote sites (lung, bladder) by fluorescence endoscopy, and [2] light-catalyzed production of toxic products in porphyrin-containing tumor cells. This study is designed to characterize tumor-localizing components of HPD, define the mechanism of tumor localization, and provide a basis for the design of improved photosensitizers, e.g., agents which can be excited at wavelengths to which pigmented tumors are not opaque, or with decreased capacity for skin photosensitization (the major adverse reaction to photoradiation therapy). Studies of absorption and fluorescence spectra, fluorescence polarization and lifetimes, and modes of porphyrincatalyzed tissue damage will be used to examine modes of cell-porphyrin interactions associated with tumor localization in vitro and in vivo. Gel chromatography and spectral studies will be used to delineate porphyrin aggregation phenomena. Reverse-phase TLC will be utilized for preliminary porphyrin characterizations. HPLC, using both UV and fluorescence detection, will be used for preparative fractionation of HPD and for more detailed analysis of pharmacokinetics of distribution, transformation and localization of porphyrins in tumor, normal tissues and plasma of the mouse.