MR molecular imaging and fluorescence microscopy for identification of activated tumor endothelium using a bimodal lipidic nanoparticle
MR molecular imaging and fluorescence microscopy for identification of activated tumor endothelium using a bimodal lipidic nanoparticle
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DOI：
10.1096/fj.05-4145fje
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发表时间：
2005-10-01
期刊：
影响因子：
4.8
通讯作者：
Nicolay, K
中科院分区：
文献类型：
--
作者：
Mulder, WJM;Strijkers, GJ;Nicolay, K
在肿瘤学研究中，非常需要基于生物分子标记物的表达水平的差异来特异性地识别肿瘤中的血管生成血管的成像技术。在血管生成级联反应中，不同的细胞表面受体，包括α v β 3-整联蛋白，在活化的内皮细胞上强烈表达。在本研究中，我们的目的是通过检测α v β 3在荷瘤小鼠的表达与磁共振成像（MRI）和荧光显微镜相结合的图像血管生成。为此，我们制备了MR可检测的荧光脂质体，每个脂质体携带类似于700个α v β 3特异性RGD肽。使用RGD竞争实验和RAD缀合的脂质体作为特异性对照。在体内，RAD脂质体和RGD脂质体都引起T-1加权MR图像上的信号增加。通过使用离体荧光显微镜确定，RGD脂质体和RAD脂质体通过不同的机制在肿瘤中积聚。RGD脂质体与活化的肿瘤内皮特异性相关，而RAD脂质体位于血管外室。这项研究表明，血管生成的MR分子成像是可行的，通过使用特定的α v β 3-整合素的靶向造影剂，和多模态成像方法提供了深入了解在肿瘤中积累的确切机制。
In oncological research, there is a great need for imaging techniques that specifically identify angiogenic blood vessels in tumors on the basis of differences in the expression level of biomolecular markers. In the angiogenic cascade, different cell surface receptors, including the alpha v beta 3-integrin, are strongly expressed on activated endothelial cells. In the present study, we aimed to image angiogenesis by detecting the expression of alpha v beta 3 in tumor bearing mice with a combination of magnetic resonance imaging (MRI) and fluorescence microscopy. To that end, we prepared MR-detectable and fluorescent liposomes, which carry similar to 700 alpha v beta 3-specific RGD peptides per liposome. RGD competition experiments and RAD-conjugated liposomes were used as controls for specificity. In vivo, both RAD liposomes and RGD liposomes gave rise to signal increase on T-1-weighted MR images. It was established by the use of ex vivo fluorescence microscopy that RGD liposomes and RAD liposomes accumulated in the tumor by different mechanisms. RGD liposomes were specifically associated with activated tumor endothelium, while RAD liposomes were located in the extravascular compartment. This study demonstrates that MR molecular imaging of angiogenesis is feasible by using a targeted contrast agent specific for the alpha v beta 3-integrin, and that the multimodality imaging approach gave insight into the exact mechanism of accumulation in the tumor.