Targeted nanoparticles for quantitative imaging of sparse molecular epitopes with MRI
Targeted nanoparticles for quantitative imaging of sparse molecular epitopes with MRI
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DOI：
10.1002/mrm.20010
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发表时间：
2004-03-01
影响因子：
3.3
通讯作者：
Wickline, SA
中科院分区：
文献类型：
--
作者：
Morawski, AM;Winter, PM;Wickline, SA
在磁共振分子成像可以应用于临床之前，必须克服某些问题，如靶细胞表面分子表位的潜在稀疏性，以及传统靶向磁共振造影剂的相对薄弱。因此，在这项研究中，研究了适用于任何已知本征弛豫度的顺磁性MRI造影剂的诊断显着性条件。一种高效的顺磁性液体全氟碳纳米颗粒造影剂(直径类似于250 nm，>；90000 Gd3+/颗粒)在1.5T下成像，并利用标准的磁共振信号模型成功地预测了实验模体中稀疏浓度的范围。此外，我们通过将抗组织因子抗体片段连接到纳米颗粒上以实现特异性结合，培养并定位了表达组织因子的单层细胞，组织因子是一种对止血和血管损伤反应至关重要的糖蛋白。对1.5T成像的细胞单层的信号进行量化，如通过建模预测的那样，在临床场强度下，只需要皮摩尔浓度的顺磁性全氟碳纳米颗粒来检测和定量组织因子。因此，对于携带高有效负载Gd的靶向顺磁性试剂，可以使用常规MRI来量化单个细胞中以皮摩尔浓度存在的分子表位。(C)2004年Wiley-Liss公司
Before molecular imaging with MRI can be applied clinically, certain problems, such as the potential sparseness of molecular epitopes on targeted cell surfaces, and the relative weakness of conventional targeted MR contrast agents, must be overcome. Accordingly, the conditions for diagnostic conspicuity that apply to any paramagnetic MRI contrast agent with known intrinsic relaxivity were examined in this study. A highly potent paramagnetic liquid perfluorocarbon nanoparticle contrast agent (similar to250 nm diameter, >90000 Gd3+/particle) was imaged at 1.5 T and used to successfully predict a range of sparse concentrations in experimental phantoms with the use of standard MR signal models. Additionally, we cultured and targeted the smooth muscle cell (SMC) monolayers that express "tissue factor," a glycoprotein of crucial significance to hemostasis and response to vascular injury, by conjugating an anti-tissue factor antibody fragment to the nanoparticles to effect specific binding. Quantification of the signal from cell monolayers imaged at 1.5 T demonstrated, as predicted via modeling, that only picomolar concentrations of paramagnetic perfluorocarbon nanoparticles were required for the detection and quantification of tissue factor at clinical field strengths. Thus, for targeted paramagnetic agents carrying high payloads of gadolinium, it Is possible to quantify molecular epitopes present in picomolar concentrations in single cells with routine MRI. (C) 2004 Wiley-Liss, Inc.