A new drug-screening procedure for photosensitizing agents used in photodynamic therapy for CNV.
A new drug-screening procedure for photosensitizing agents used in photodynamic therapy for CNV.
复制标题
DOI：
--
复制
发表时间：
2001
影响因子：
4.4
通讯作者：
Norbert Lange;J. Ballini;G. Wagnières;H. Bergh
中科院分区：
文献类型：
--
作者：
Norbert Lange;J. Ballini;G. Wagnières;H. Bergh
由于光动力疗法（photodynamic therapy，PDT）可导致脉络膜新生血管（choroidal neovascularization，CNV）的形成，因此PDT已成功用于治疗年龄相关性黄斑变性（age-related vascular degeneration，AMD）的CNV。然而，大多数传统的光敏剂，主要开发用于肿瘤PDT，缺乏对靶向新血管形成的选择性。已经开发了用于治疗与AMD相关的CNV的新光敏剂的药物筛选的实验模型。它包括将光敏剂和荧光染料静脉内（IV）注射到鸡的绒毛尿囊膜（CAM）中，然后测量荧光药代动力学、血管系统渗漏和光血栓功效。方法将受精卵置于荧光显微镜下观察。静脉注射不同染料后，进行时间依赖性荧光血管造影。PDT后24小时通过荧光血管造影评估PDT参数的效果。结果尽管亲脂性苯并卟啉衍生物单酸环A（BPD-MA）的荧光在血管内持续2 h，但亲水性染料倾向于通过有孔新生血管渗漏。通过改变PDT参数，血管损伤可以指向PDT后24小时测量的直径小于10微米的血管的闭合。高光敏剂浓度和高光剂量在60分钟内导致血流停滞，通过荧光血管造影术证实。结论：荧光血管造影和PDT静脉注射到CAM后显示出很强的相似性，在临床试验中获得的结果PDT CNV与AMD。因此，该模型可以提供关于PDT机制的有价值的信息，并且可以用于药物筛选目的，以开发用于CNV的PDT的改进的致敏剂。
PURPOSE Because vascular occlusion has been observed as a consequence of photodynamic therapy (PDT), this method has been successfully used for the treatment of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). However, most conventional photosensitizers, primarily developed for tumor PDT, lack selectivity for the targeting of neovascularization. An experimental model has been developed for drug screening of new photosensitizers for the treatment of CNV associated with AMD. It consists of intravenous (IV) injection of photosensitizers and fluorescent dyes into the chick's chorioallantoic membrane (CAM), followed by measurement of fluorescence pharmacokinetics, leakage from the vascular system, and photothrombic efficacy. METHODS Fertilized chicken eggs were placed under a fluorescence microscope. After intravenous injection of different dyes, time-dependent fluorescence angiography was performed. The effect of PDT parameters was assessed by fluorescence angiography 24 hours after PDT. RESULTS Although fluorescence of lipophilic benzoporphyrin derivative monoacid ring A (BPD-MA) remained intravascular during 2 hours, hydrophilic dyes tended to leak through the fenestrated neovascularization. By variation of PDT parameters, vascular damage could be directed toward closure of vessels with a diameter smaller than 10 microm, as measured 24 hours after PDT. High photosensitizer concentrations and high light doses resulted in blood flow stasis within 60 minutes, confirmed by fluorescence angiography. CONCLUSIONS Fluorescence angiography and PDT after IV injection into the CAM showed strong similarities to results obtained in clinical tests of PDT in CNV associated with AMD. Thus, this model can provide valuable information about PDT mechanisms and can be used for drug-screening purposes in development of improved sensitizers for the PDT of CNV.