PORPHYRIN PHOTOSENSITIZATION AND ANTINEOPLASTIC PHOTOTHE

选择性根治肿瘤性病变，对 正常宿主组织，一直是抗肿瘤化疗的目标。肿瘤 由血卟啉衍生的卟啉混合物的光敏化作用， 并被称为HPD(血卟啉衍生物)，可以显示这种程度 选择性。该项目旨在阐明以下决定因素 卟啉及其相关结构化合物对肿瘤的定位。这个 长期目标是改善肿瘤的定位和光疗， 例如通过提供可在光波长处被激活的染料来 哪些组织是透明的，同时最大限度地减少短暂的皮肤 伴随着当前程序的光敏化。我们有 确定HPD的活性成分为二聚体和三聚体 血卟啉酯。实验证据表明这些幽门螺杆菌 酯与血浆蛋白和脂蛋白结合，随后 分布部分由脂蛋白的相对数量决定 不同组织中的受体。血卟啉的其他酯可以是 使用任何含游离羧基的卟啉或类似结构制备的 一群人。我们计划[1]在酯分子中加入一部分 其他所需的特性，例如在近红外光谱中的强吸收。 [2]研究脂蛋白-受体模型作为肿瘤的决定因素 本地化。[3]探索荧光产量和光动力毒性 一种卟啉结构的功能。[4]测量卟啉与 肿瘤与皮肤，作为时间和卟啉结构的函数。卟啉类化合物 通过加州大学戴维斯分校的分包合同提供 为新代理的定向设计提供了一种方法 为提高临床光疗水平而努力。

The selective eradication of neoplastic lesions, with minimal damage to normal host tissues, has been the goal of antitumor chemotherapy. Tumor photosensitization by a mixture of porphyrins derived from hematoporphyrin, and termed HPD (hematoporphyrin derivative), can display this degree of selectivity. This project is designed to elucidate the determinants of tumor localization by porphyrins and compounds of related structure. The long-term goal is the improvement of tumor-localization and phototherapy, e.g., by providing dyes which can be activated at wavelengths of light to which tissues are transparent, while minimizing the transient skin photosensitization which accompanies the current procedure. We have determined that the active components of HPD are dimeric and trimeric hematoporphyrin esters. Experimental evidence suggests that these HP esters bind to both plasma protein and lipoprotein, with subsequent distribution determined, in part, by the relative numbers of lipoprotein receptors in different tissues. Other esters of hematoporphyrin can be prepared using any porphyrin or analogous structure with a free carboxyl group. We plan to [1] incorporate into the ester molecule a moiety with other desirable characteristics, e.g., strong absorption in the near IR. [2] Examine the lipoprotein-receptor model as a determinant of tumor localization. [3] Explore fluorescence yields and photodynamic toxicity as a function of porphyrin structure. [4] Measure binding of porphyrins to tumor vs. skin, as a function of time and porphyrin structure. Porphyrins provided via a sub-contract at the University of California (Davis) will represent an approach to the directed design of new agents with a view toward the improvement of clinical phototherapy.