Anderson S A, Rader R K, Westlin W F, Null C, Jackson D, Lanza G M, Wickline S A, Kotyk J J
Monsanto Company, St. Louis, Missouri, USA.
Magn Reson Med. 2000 Sep;44(3):433-9. doi: 10.1002/1522-2594(200009)44:3<433::aid-mrm14>3.0.co;2-9.
Site-directed contrast enhancement of angiogenic vessels in vivo was demonstrated using antibody targeting of an MRI contrast agent to the alpha(v)beta(3) integrin, a molecular marker characteristic of angiogenic endothelium. The agent was tested in a rabbit corneal micropocket model, in which neovasculature is induced in the cornea using basic fibroblast growth factor. The targeted contrast agent consists of Gd-perfluorocarbon nanoparticles linked to alpha(v)beta(3) integrin antibody DM101. The animal group receiving the targeted contrast agent displayed a 25% increase in the average MR signal intensity after 90 min. Control groups in which the nanoparticles are either used alone, linked to an isotype-matched antibody, or linked to DM101 and administered following receptor blocking did not display MR contrast enhancement at similar dose levels. These findings indicate that the antibody-targeted agent enhances MR signal intensity in the capillary bed in a corneal micropocket model of angiogenesis, and is selectively retained within the angiogenic region via specific interaction with the alpha(v)beta(3) epitope.
利用针对MRI造影剂与α(v)β(3)整合素(一种血管生成内皮细胞特有的分子标记物)的抗体靶向作用,在体内实现了对血管生成血管的定点对比增强。该造影剂在兔角膜微囊模型中进行了测试,在该模型中使用碱性成纤维细胞生长因子诱导角膜新生血管形成。靶向造影剂由与α(v)β(3)整合素抗体DM101连接的钆全氟碳纳米颗粒组成。接受靶向造影剂的动物组在90分钟后平均MR信号强度增加了25%。纳米颗粒单独使用、与同型匹配抗体连接或与DM101连接并在受体阻断后给药的对照组在相似剂量水平下未显示MR对比增强。这些发现表明,在角膜微囊血管生成模型中,抗体靶向剂可增强毛细血管床中的MR信号强度,并通过与α(v)β(3)表位的特异性相互作用选择性地保留在血管生成区域内。