PDT--MECHANISMS AND STRATEGIES FOR OPTIMIZATION

本计划项目的长期总体目标是增加 对光敏剂构效关系的理解 用于光动力疗法的阴离子和阳离子，以及体外和体内 它们作用的活体机制。派生出的机械性信息将 被用来制定策略以提高……的效率 光动力/光化学疗法。这将通过以下方式实现 以下是个人研究项目： 1.具有特定增量结构变化的新型阴离子光敏剂 并将合成和制造长波吸收光敏剂 可用于其他项目。它们的光物理性质 将测定增感剂和比较增感剂的概念 效率将得到提高。 2.新型光敏剂的构效关系为 关于肿瘤细胞和血管的决定因素的定义 光敏化。井中肿瘤灌注量与细胞光敏性的关系 并对血流不佳的肿瘤区域进行评估。局部性和系统性 寄主对光敏剂和光动力处理的反应机制 被研究。 3.新型阳离子光敏剂的合成及结构活性 丹参的体内外作用机制及其相互关系 将对光毒性进行定义。多药物治疗和联合治疗 将设计治疗方法来提高光化学疗法的疗效。 4.人体肿瘤光动力治疗反应的动态变化 将研究，包括增敏剂的摄取，血管的时间框架 反应、光漂白和以前治疗的效果。 个人研究项目将得到两个非常重要的项目的支持 技术核心组件--一个用于药物评价和流式细胞仪， 一个用于光学方面的研究和非侵入性监测 治疗进展。这些都是确保全面进步和 生产力。完成生物数学和管理核心组件 这个多学科项目。

It is the long term, overall goal of this Program Project to increase the understanding of structure-activity relationships of photosensitizers, both anionic and cationic, used in photodynamic therapy, and the in vitro and in vivo mechanisms of their action. The mechanistic information derived will be used to devise strategies to improve the efficacy of photodynamic/photochemotherapy. This will be achieved through the following Individual Research Projects: 1. New anionic photosensitizers of specific incremental structural changes and long-wavelength absorbing photosensitizers will be synthesized and made available to other projects. The photophysical properties of these sensitizers will be determined and a concept for comparison of sensitizer efficiency will be developed. 2. Structure/activity relationships of novel photosensitizers will be defined with regard to the determinants for tumor cell and vascular photosensitization. Tumor perfusion and photosensitivity of cells in well and poorly perfused tumor regions will be assessed. Local and systemic host response mechanisms to photosensitizer and photodynamic treatment will be studied. 3. New cationic photosensitizers will be synthesized and structure-activity relationships and mechanisms of in vitro and in vivo mechanisms of phototoxicity will be defined. Multiagent treatments and combination treatments will be devised to enhance the efficacy of photochemotherapy. 4. The dynamics of the response to photodynamic therapy of human tumors will be studied, including sensitizer uptake, time frame of vascular response, photobleaching and effects of previous treatments. The Individual Research Projects will be supported by two very important technical core components -- one for drug evaluation and flow cytometry, one for optical aspects of the research and non-invasive monitoring of treatment progress. These are critical to ensure overall progress and productivity. Biomathematics and administrative core components complete this multi-disciplinary Program Project.