Ultrasonic Analysis of Peptide-and Antibody-Targeted Microbubble Contrast Agents for Molecular Imaging of αVβ3-Expressing Cells
Ultrasonic Analysis of Peptide-and Antibody-Targeted Microbubble Contrast Agents for Molecular Imaging of αVβ3-Expressing Cells
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DOI：
10.1162/1535350041464883
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发表时间：
2004-04-01
影响因子：
2.8
通讯作者：
Ferrara, Katherine W.
中科院分区：
文献类型：
--
作者：
Dayton, Paul A.;Pearson, David;Ferrara, Katherine W.
靶向超声造影剂的目标是显著和选择性地增强靶向血管部位的检测。在这篇手稿中，三种不同的造影剂针对α（v β 3）整联蛋白进行检查。α（v）β（3）整联蛋白已被证明在新生血管形成期间在转移性肿瘤和内皮细胞上高度表达，并且其表达已被证明与肿瘤分级相关。这些造影剂与表达α（v）β（3）的细胞单层的特异性粘附在体外得到证实，并与非靶向药物进行了比较。声学研究表明，暴露于靶向造影剂的单层的后向散射振幅增加高达13倍（22 dB），相对于对照气泡的增强。对于结合剂，观察到回波幅度和气泡浓度之间的线性关系。从粘附的靶向剂的回声的去相关被观察到作为声压和气泡密度的函数的连续脉冲。频域分析表明，粘附的靶向气泡表现出高振幅窄带回波分量，与自由微泡的主要宽带响应相反。结果表明，粘附的靶向造影剂与自由漂浮的微泡是可区分的，靶向造影剂在血管生成检测中提供更高的灵敏度，并且常规超声成像技术如信号相减或去相关检测可用于检测具有足够信噪比的表达整合素的脉管系统。Mol Imaging（2004）3，125-134.
The goal of targeted ultrasound contrast agents is to significantly and selectively enhance the detection of a targeted vascular site. In this manuscript, three distinct contrast agents targeted to the alpha(v beta 3) integrin are examined. The alpha(v)beta(3) integrin has been shown to be highly expressed on metastatic tumors and endothelial cells during neovascularization, and its expression has been shown to correlate with tumor grade. Specific adhesion of these contrast agents to alpha(v)beta(3)-expressing cell monolayers is demonstrated in vitro, and compared with that of nontargeted agents. Acoustic studies illustrate a backscatter amplitude increase from monolayers exposed to the targeted contrast agents of up to 13-fold (22 dB) relative to enhancement due to control bubbles. A linear dependence between the echo amplitude and bubble concentration was observed for bound agents. The decorrelation of the echo from adherent targeted agents is observed over successive pulses as a function of acoustic pressure and bubble density. Frequency-domain analysis demonstrates that adherent targeted bubbles exhibit high-amplitude narrowband echo components, in contrast to the primarily wideband response from free microbubbles. Results suggest that adherent targeted contrast agents are differentiable from free-floating microbubbles, that targeted contrast agents provide higher sensitivity in the detection of angiogenesis, and that conventional ultrasound imaging techniques such as signal subtraction or decorrelation detection can be used to detect integrin-expressing vasculature with sufficient signal-to-noise. Mol Imaging (2004) 3, 125-134.