PDT with TOOKAD® studied in the chorioallantoic membrane of fertilized eggs
PDT with TOOKAD® studied in the chorioallantoic membrane of fertilized eggs
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DOI：
10.1016/s1572-1000(05)00006-2
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发表时间：
2005-03-01
影响因子：
3.3
通讯作者：
Steiner, Rudolf
中科院分区：
文献类型：
--
作者：
Rueck, Angelika;Boehmler, Andrea;Steiner, Rudolf
背景：TOOKAD（R）PDT治疗血管的潜在应用进行了研究。TOOKAD（R）（WST 09）是一种新型的钯-细菌脱镁叶绿酸，在近红外吸收光，具有高的系间交叉量子产率。我们的研究评估了这种药物在诱导血管损伤方面的疗效，以期其可能用于治疗年龄相关性黄斑degeneration.Methods：在受精卵绒毛尿囊膜的新生血管中研究TOOKAD（R）-PDT的血管损伤。通过视频显微镜和激光扫描显微镜进行药代动力学研究。结果：TOOKAD（R）在注射后的最初几分钟内在血管中积累。TOOKAD（R）荧光主要见于管腔，而非血管内皮层。虽然荧光非常弱，但从循环中的荧光光谱可以将其归因于TOOKAD（R）。在施加763 nm光后24小时进行损伤评估。不同短药光间隔（1-10 min）对细胞损伤程度无显著性差异，但损伤程度随光能剂量的增加而增加。用5 J/cm（2）和33 μ g/胚胎的TOOKAD（R）剂量照射，可以闭合较小的血管和消失的毛细血管，相当于0.0062的光毒性效应。从这项工作中讨论的结果来看，TOOKAD（R）可能是年龄PDT的潜在药物-脉络膜中新血管的生长可导致视力丧失。(C)2005 Elsevier B. V.保留所有权利。
Background: The potential application of TOOKAD (R) PDT for the treatment of blood vessels was investigated. TOOKAD (R) (WST09), a novel palladium-bacteriopheophorbide absorbs light in the near IR with a high quantum yield of intersystem crossing. Our study assessed the efficacy of this drug in inducing vascular damage with a view to its possible use in the treatment of age-related macular degeneration.Methods: Vascular damage of TOOKAD (R) -PDT was studied in neovessels of the chorioallantoic membrane of fertilized eggs. Pharmacokinetic investigations were done by video microscopy and laser scanning microscopy. To induce damage vessels were irradiated with 763 nm light from a diode laser.Results: TOOKAD (R) was accumulated in the vessels in the first minutes following injection. TOOKAD (R) fluorescence was seen predominantly in the lumen and not in the vascular endothelial layer. Although fluorescence was very weak it could be attributed to TOOKAD (R) from the fluorescence spectrum in the circulation. Damage assessment was done 24 h after application of 763 nm light. No significant difference in the degree of damage was observed with different short drug-light intervals (1-10 min), but damage increased with the light energy dose. Closure of smaller vessels and vanished capillaries could be achieved by irradiation with 5 J/cm(2) and a TOOKAD (R) dose of 33 mu g/embryo, corresponding to a phototoxic efficacy of 0.0062.Conclusions: From the results discussed in this work, TOOKAD (R) could be a potential drug for the PDT of age-related macular degeneration in which the growth of new vessels in the choroids can lead to loss of vision. (C) 2005 Elsevier B.V. All rights reserved.