MODE OF ACTION OF THE PHOTO-ACTIVATED PORPHYRINS

HPD是一种来自血卟啉的卟啉的复杂混合物， 可用于实体瘤的定位和治疗。 定位结果 肿瘤选择性保留HPD成分，但不 相邻正常组织，在给药后48小时内。 HPD的临床实用性基于[1]远程肿瘤定位 通过荧光内窥镜检查部位（肺、膀胱），以及[2]光催化 在含有卟啉的肿瘤细胞中产生有毒产物。 这 研究旨在表征HPD的肿瘤定位组分， 明确肿瘤定位的机制，为肿瘤的治疗提供依据。 设计改进的光敏剂，例如，可以被激发的试剂， 色素肿瘤不透明的波长，或减少 皮肤光敏化能力（主要不良反应， 光辐射疗法）。 吸收光谱和荧光光谱的研究， 荧光偏振和寿命，以及卟啉催化的模式 组织损伤将被用于检查细胞-卟啉相互作用的模式 与体外和体内肿瘤定位相关。 凝胶 色谱和光谱研究将用于描绘卟啉 聚集现象 将使用反相TLC进行初步分析。 卟啉表征。 HPLC，使用UV和荧光 检测，将用于HPD的制备分馏和更多 详细分析分布、转化和 卟啉在小鼠肿瘤、正常组织和血浆中的定位。

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.