OXYGEN AND LIGHT DEPENDENCY OF PHOTODYNAMIC THERAPY

光动力疗法（PDT）的有效性取决于 肿瘤组织中同时存在光敏剂， 氧气和光。 在卟啉介导的PDT中， 可以在低光敏剂水平下通过相对非- 选择性血管塌陷和局部缺血。 直接光动力学 然而，肿瘤细胞灭活可能受到快速的 血管损伤和肿瘤缺氧的发展。 它是漫长的- 本申请的长期目标是分析 PDT肿瘤中直接肿瘤细胞效应和血管效应之间的关系 破坏，并调查导致破坏的原因。 这些影响。 据推测，这将有利于 PDT治疗的选择性和有效性，以确定 肿瘤破坏的机制可以从 血管效应直接作用于肿瘤细胞。 到 为了评估这一假设的有效性，以下研究将 执行： 各种新开发的光敏剂（酞菁， 叶绿素，阳离子染料）将研究建立在 体内/体外方法，就其直接 体内光动力肿瘤细胞灭活，以及用于 血管损伤和诱导组织缺氧。 可能参与血管PDT损伤的发展 花生四烯酸代谢物，一组主要的血管活性物质， 炎症介质，将通过体外和体内研究 体内方法 前列腺素的光动力释放， 前列环素、血栓素和白三烯形成巨噬细胞、肿瘤， 将测量内皮细胞和平滑肌细胞以及血小板 用放射免疫法 保护组织免受PDT诱导的血管损伤的可能性， 给予花生四烯酸抑制剂的炎症作用 酸性代谢产物（环氧合酶和脂氧合酶 抑制剂）将被测试。 这种治疗对肿瘤的影响 将评估PDT的反应。

The effectiveness of photodynamic therapy (PDT) depends on the simultaneous presence in the tumor tissue of photosensitizer, oxygen and light. In porphyrin-mediated PDT, tumor destruction can be achieved at low photosensitizer levels via relatively non- selective vascular collapse and ischemia. Direct photodynamic tumor cell inactivation, however, can be limited by the rapid vascular damage and development of tumor hypoxia. It is the long- term objective of this application to analyze the relationship between direct tumor cell effects and vascular effects in PDT tumor destruction, as well as to investigate the causes which lead to these effects. It is hypothesized that it would be beneficial for PDT treatment selectivity and effectiveness to identify ways by which the mechanism of tumor destruction could be shifted away from vascular effects towards a direct action upon tumor cells. To assess the validity of this hypothesis, the following studies will be carried out: Various newly developed photosensitizer (phthalocyanines, chlorophylls, cationic dyes) will be studied by established in vivo/in vitro methods with respect to their potential for direct photodynamic tumor cell inactivation in vivo, as well as for vascular damage and induction of tissue hypoxia. The possible involvement in the development of vascular PDT damage of arachidonic acid metabolites, a group of major vasoactive, inflammatory mediators, will be investigated by in vitro and in vivo methods. The photodynamic release of prostaglandin, prostacyclin, thromboxane and leukotrienes form macrophages, tumor, endothelial and smooth muscle cells, and platelets will be measured by radioimmunoassay. The possibility of protecting tissue from PDT-induced vascular and inflammatory effects by administration of inhibitors of arachidonic acid metabolite production (cyclooxgenase and lipoxygenase inhibitors) will be tested. The effects of such treatment on tumor response to PDT will be assessed.