Cell-permeable MR contrast agents with increased intracellular retention.
Cell-permeable MR contrast agents with increased intracellular retention.
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DOI：
10.1021/bc8002919
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发表时间：
2008-10
影响因子：
4.7
通讯作者：
Meade, Thomas J.
中科院分区：
文献类型：
--
作者：
Endres, Paul J.;MacRenaris, Keith W.;Vogt, Stefan;Meade, Thomas J.
磁共振成像（MRI）是一种在临床和实验环境中使用的技术，用于在没有电离辐射的情况下产生不透明生物体的高分辨率图像。目前，MR成像通过造影剂增强，并且这些小分子Gd（III）螯合物绝大多数局限于细胞外区域。结果，造影剂局限于血管区域，降低了它们提供关于细胞生理学或分子病理学的信息的能力。我们已经表明，精氨酸的多肽具有跨细胞膜转运Gd（III）造影剂的能力。然而，这种转运不是单向的，一旦进入细胞内，甘氨酸修饰的造影剂就会迅速流出，降低细胞内Gd（III）浓度和相应的MR图像强度。通过利用细胞固有的二硫键还原环境，硫醇化合物Gd（III）-DOTA-SS-Arg 8和Gd（III）-DTPA-SS-Arg 8在细胞内化时从其细胞穿透肽转导结构域裂解。该反应通过将螯合的Gd（III）从细胞转导结构域切割出来，延长了其与细胞相关的寿命。
Magnetic resonance imaging (MRI) is a technique used in both clinical and experimental settings to produce high resolution images of opaque organisms without ionizing radiation. Currently, MR imaging is augmented by contrast agents and the vast majority these small molecule Gd(III) chelates are confined to the extracellular regions. As a result, contrast agents are confined to vascular regions reducing their ability to provide information about cell physiology or molecular pathology. We have shown that polypeptides of arginine have the capacity to transport Gd(III) contrast agents across cell membranes. However, this transport is not unidirectional and once inside the cell the arginine-modified contrast agents efflux rapidly, decreasing the intracellular Gd(III) concentration and corresponding MR image intensity. By exploiting the inherent disulfide reducing environment of cells, thiol compounds, Gd(III)-DOTA-SS-Arg8 and Gd(III)-DTPA-SS-Arg8, are cleaved from their cell penetrating peptide transduction domains upon cell internalization. This reaction prolongs the cell-associated lifetime of the chelated Gd(III) by cleaving it from the cell transduction domain.
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影响因子：
--
作者：
Allen, MJ;MacRenaris, KW;Meade, TJ
通讯作者：
Meade, TJ
影响因子：
4.7
作者：
Ebright, YW;Chen, Y;Ebright, RH
通讯作者：
Ebright, RH
影响因子：
4.3
作者：
Botta, M;Aime, S;Terreno, E
通讯作者：
Terreno, E
影响因子：
4.7
作者：
Han, G;Chari, NS;Rotello, VM
通讯作者：
Rotello, VM
影响因子：
4
作者：
Carrera, Carla;Digilio, Giuseppe;Aime, Silvio
通讯作者：
Aime, Silvio