Molecular imaging of VEGF receptors in angiogenic vasculature with single-chain VEGF-based probes
Molecular imaging of VEGF receptors in angiogenic vasculature with single-chain VEGF-based probes
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DOI：
10.1038/nm1522
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发表时间：
2007-04-01
期刊：
影响因子：
82.9
通讯作者：
Backer, Joseph M.
中科院分区：
文献类型：
--
作者：
Backer, Marina V.;Levashova, Zoya;Backer, Joseph M.
我们描述了新一代蛋白质靶向造影剂，用于血管内皮生长因子（VEGF）细胞表面受体的多模态成像。这些受体在血管生成中发挥关键作用，是药物开发的重要靶点。我们的探针基于用含半胱氨酸标签表达的单链重组 VEGF，允许使用造影剂进行位点特异性标记，用于近红外荧光成像、单光子发射计算机断层扫描或正电子发射断层扫描。这些探针在体外保留 VEGF 活性，并在体内选择性且高度特异性地集中摄取到肿瘤的脉管系统和周围宿主组织中。荧光造影剂显示出长期持久性并与内皮细胞标记物共定位，表明内化是由受体介导的。我们预计使用这些探针对 VEGF 受体进行多模态成像将有助于临床诊断和治疗监测，并将有助于加速新的血管生成导向药物和治疗的开发。
We describe a new generation of protein-targeted contrast agents for multimodal imaging of the cell-surface receptors for vascular endothelial growth factor (VEGF). These receptors have a key role in angiogenesis and are important targets for drug development. Our probes are based on a single-chain recombinant VEGF expressed with a cysteine-containing tag that allows site-specific labeling with contrast agents for near-infrared fluorescence imaging, single-photon emission computed tomography or positron emission tomography. These probes retain VEGF activities in vitro and undergo selective and highly specific focal uptake into the vasculature of tumors and surrounding host tissue in vivo. The fluorescence contrast agent shows long-term persistence and co-localizes with endothelial cell markers, indicating that internalization is mediated by the receptors. We expect that multimodal imaging of VEGF receptors with these probes will be useful for clinical diagnosis and therapeutic monitoring, and will help to accelerate the development of new angiogenesis-directed drugs and treatments.