Three-dimensional MR mapping of angiogenesis with α5β1(αvβ3)-targeted theranostic nanoparticles in the MDA-MB-435 xenograft mouse model
Three-dimensional MR mapping of angiogenesis with α5β1(αvβ3)-targeted theranostic nanoparticles in the MDA-MB-435 xenograft mouse model
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DOI：
10.1096/fj.08-112060
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发表时间：
2008-12-01
期刊：
影响因子：
4.8
通讯作者：
Lanza, Gregory M.
中科院分区：
文献类型：
--
作者：
Schmieder, Anne H.;Caruthers, Shelton D.;Lanza, Gregory M.
我们的目的是1）使用α（5）β（1）（RGD）-或不相关的RGS-靶向顺磁性纳米颗粒，通过三维（3D）MR分子成像表征MDA-MB-435异种移植小鼠模型中的血管生成，和2）使用MR分子成像评估α（5）β（1）（α（v）β（3））-与α（v）β（3）-靶向烟曲霉素的抗血管生成有效性（50 μ g/kg）纳米颗粒。在施用α（5）β（1）（RGD）或不相关的RGS-顺磁性纳米颗粒之前和之后，用MR对荷瘤小鼠进行成像。在实验2中，小鼠在肿瘤植入后第7、11、15和19天接受盐水或α（5）β（1）（α（v）β（3））-或α（v）β（3）-靶向烟曲霉素纳米颗粒。在第22天，使用α（5）β（1）（α（v）β（3））靶向顺磁性纳米颗粒进行MRI以监测抗血管生成反应。α 5 β 1（RGD）信号增强的三维重建显示肿瘤周围沿着稀疏、不对称的血管生成模式，占肿瘤表面积的2.0%。与FITC-凝集素共定位的α（5）β（1）靶向罗丹明纳米颗粒证实了外周新生血管信号。与对照组相比，α（5）β（1）（α（v）β（3））-烟曲霉素纳米颗粒可将新生血管减少至可忽略的水平; α（v）β（3）-靶向烟曲霉素纳米颗粒的效果较差（P > 0.05）。MDA-MB-435肿瘤中的血管生成从低水平减少到可忽略不计的水平并没有减少肿瘤体积。MR分子成像可用于表征具有稀疏新生血管的肿瘤，这些肿瘤不太可能对靶向抗血管生成治疗具有降低的生长反应。
Our objectives were 1) to characterize angiogenesis in the MDA-MB-435 xenograft mouse model with three-dimensional (3D) MR molecular imaging using alpha(5)beta(1)(RGD)- or irrelevant RGS-targeted paramagnetic nanoparticles and 2) to use MR molecular imaging to assess the antiangiogenic effectiveness of alpha(5)beta(1)(alpha(v)beta(3))- vs. alpha(v)beta(3)-targeted fumagillin (50 mu g/kg) nanoparticles. Tumor-bearing mice were imaged with MR before and after administration of either alpha(5)beta(1)(RGD) or irrelevant RGS-paramagnetic nanoparticles. In experiment 2, mice received saline or alpha(5)beta(1)(alpha(v)beta(3))- or alpha(v)beta(3)-targeted fumagillin nanoparticles on days 7, 11, 15, and 19 posttumor implant. On day 22, MRI was performed using alpha(5)beta(1)(alpha(v)beta(3))-targeted paramagnetic nanoparticles to monitor the antiangiogenic response. 3D reconstructions of alpha(5)beta(1)(RGD)-signal enhancement revealed a sparse, asymmetrical pattern of angiogenesis along the tumor periphery, which occupied < 2.0% tumor surface area. alpha(5)beta(1)-targeted rhodamine nanoparticles colocalized with FITC-lectin corroborated the peripheral neovascular signal. alpha(5)beta(1)(alpha(v)beta(3))-fumagillin nanoparticles decreased neovasculature to negligible levels relative to control; alpha(v)beta(3)-targeted fumagillin nanoparticles were less effective (P > 0.05). Reduction of angiogenesis in MDA-MB-435 tumors from low to negligible levels did not decrease tumor volume. MR molecular imaging may be useful for characterizing tumors with sparse neovasculature that are unlikely to have a reduced growth response to targeted antiangiogenic therapy.