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光动力治疗药物光点光敏剂MV6401(甲基脱镁叶绿酸铟氯化物)在灵长类脉络膜毛细血管和激光诱导的脉络膜新生血管中的评估。

Evaluation of photopoint photosensitizer mv6401, indium chloride methyl pyropheophorbide, as a photodynamic therapy agent in primate choriocapillaris and laser-induced choroidal neovascularization.

作者信息

Ciulla Thomas A, Criswell Mark H, Danis Ronald P, Snyder Wendy J, Small Ward

机构信息

Retina Service Research Laboratories, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana 46260, USA.

出版信息

Retina. 2004 Aug;24(4):521-9. doi: 10.1097/00006982-200408000-00004.

DOI:10.1097/00006982-200408000-00004
PMID:15300072
Abstract

PURPOSE

To assess the potential of a new photosensitizer, indium chloride methyl pyropheophorbide (PhotoPoint MV6401), for ocular photodynamic therapy (PDT) in normal choriocapillaris vessels and experimentally induced choroidal neovascularization in New-World monkeys (Saimiri sciureus).

METHODS

PhotoPoint MV6401 (Miravant Pharmaceuticals, Inc., Santa Barbara, CA) was activated at 664 nm using a DD3-0665 (Miravant Systems, Inc., Santa Barbara, CA) 0.5 W diode laser. The efficacy of MV6401 was evaluated by indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. The drug and light doses were 0.10 micromoles/kg to 0.3 micromoles/kg and 10 J/cm to 40 J/cm, respectively, and post-injection activation times ranged from +10 minutes to +120 minutes.

RESULTS

Best closure of normal choriocapillaris was achieved at a dosage level of 0.15 micromoles/kg in primates. Histology demonstrated that increased post-injection activation times (+60 minutes to +90 minutes) and low laser light doses (10 J/cm to 20 J/cm) in the primate model resulted in selective closure of the choriocapillaris and medium sized choroidal vessels with minimal effect to the retina. Histology from neovascular lesions PDT-treated with MV6401 revealed significant diminution of vascularity, correlating with diminution of leakage observed on angiography.

CONCLUSION

PhotoPoint MV6401, indium chloride methyl pyropheophorbide, is a potent photosensitizer that demonstrates both efficacy and selectivity in primate choriocapillaris and laser-induced choroidal neovascularization occlusion. Maximum selectivity was achieved using a post infusion interval of +60 to +90 minutes.

摘要

目的

评估一种新型光敏剂——甲基脱镁叶绿酸铟氯化物(PhotoPoint MV6401)在新世界猴(松鼠猴,Saimiri sciureus)正常脉络膜毛细血管以及实验性诱导的脉络膜新生血管中的眼内光动力疗法(PDT)潜力。

方法

使用DD3 - 0665(Miravant Systems公司,加利福尼亚州圣巴巴拉)0.5瓦二极管激光器在664纳米波长下激活PhotoPoint MV6401(Miravant Pharmaceuticals公司,加利福尼亚州圣巴巴拉)。通过间接检眼镜检查、眼底摄影、荧光素血管造影和组织学评估MV6401的疗效。药物剂量和光剂量分别为0.10微摩尔/千克至0.3微摩尔/千克以及10焦/平方厘米至40焦/平方厘米,注射后激活时间范围为+10分钟至+120分钟。

结果

在灵长类动物中,剂量水平为0.15微摩尔/千克时正常脉络膜毛细血管实现了最佳闭合。组织学显示,在灵长类动物模型中,注射后激活时间增加(+60分钟至+90分钟)以及低激光光剂量(10焦/平方厘米至20焦/平方厘米)导致脉络膜毛细血管和中等大小脉络膜血管选择性闭合,对视网膜影响最小。用MV6401进行PDT治疗的新生血管病变的组织学显示血管显著减少,这与血管造影中观察到的渗漏减少相关。

结论

甲基脱镁叶绿酸铟氯化物PhotoPoint MV6401是一种有效的光敏剂,在灵长类动物脉络膜毛细血管和激光诱导的脉络膜新生血管闭塞中均显示出疗效和选择性。使用+60至+90分钟的输注后间隔可实现最大选择性。

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