Schmidt-Erfurth U, Hasan T, Flotte T, Gragoudas E, Birngruber R
Augenklinik, Medizinische Universität, Lübeck.
Ophthalmologe. 1994 Jun;91(3):348-56.
Photodynamic therapy (PDT) with its potential for precise localization and absence of severe side effects such as radiation retinopathy may be particularly appropriate for the treatment of intraocular tumors. Benzoporphyrin (BPD), a potent photosensitizer currently in clinical trial, absorbs light at 692 nm, thus allowing sufficient tissue penetration due to minor light absorption in melanin and hemoglobin. The efficiency and selectivity of BPD are significantly pronounced through preassociation with low-density lipoprotein (LDL), since proliferating cells exhibit an increased metabolism of lipoproteins. As an experimental model Greene's melanomas were implanted either into the iris or choroid of albino rabbits. Irradiation at a radiation energy of 80 for iris and 100 J/cm2 for choroidal tumors 3 h after the i.v. injection of BPD-LDL (2 mg/kg) was administered via a laser arrangement with argon-pumped dye-laser, using the slit-lamp. Angiographies and LM/EM histologies were done immediately, and 1, 3, and 14-21 days post-exposure. All 16 treated tumors demonstrated complete regression with a remaining avascular, fibrotic scar. Immediate vascular occlusion within the tumor was seen angiographically, suggesting a direct vascular mechanism. Histologically, two primary mechanisms could be detected: destruction of neovascular endothelial cells and intracellular tumor cell damage. These results indicate that PDT using BPD-LDL complexes may provide an efficient and selective modality for the management of intraocular neoplasms. The availability of new and potent photosensitizers may also lead to broader clinical applications.
光动力疗法(PDT)因其具有精确定位的潜力且不存在诸如放射性视网膜病变等严重副作用,可能特别适用于眼内肿瘤的治疗。苯并卟啉(BPD)是一种目前正在进行临床试验的强效光敏剂,它在692nm波长处吸收光,由于其在黑色素和血红蛋白中的光吸收较少,从而能够实现足够的组织穿透。通过与低密度脂蛋白(LDL)预结合,BPD的效率和选择性得到显著提高,因为增殖细胞表现出脂蛋白代谢增加。以白化兔为实验模型,将格林氏黑色素瘤植入虹膜或脉络膜。在静脉注射BPD-LDL(2mg/kg)3小时后,使用氩泵浦染料激光通过裂隙灯进行照射,虹膜照射的辐射能量为80J/cm²,脉络膜肿瘤照射的辐射能量为100J/cm²。在照射后立即以及照射后1天、3天和14 - 21天进行血管造影和光镜/电镜组织学检查。所有16个接受治疗的肿瘤均显示完全消退,留下无血管的纤维化瘢痕。血管造影显示肿瘤内立即出现血管闭塞,提示存在直接的血管机制。组织学检查可发现两种主要机制:新生血管内皮细胞的破坏和肿瘤细胞内损伤。这些结果表明,使用BPD-LDL复合物的光动力疗法可能为眼内肿瘤的治疗提供一种高效且选择性的方法。新型强效光敏剂的出现也可能带来更广泛的临床应用。