Quantitative Analysis of HER2 Receptor Expression In Vivo by Near-Infrared Optical Imaging
Quantitative Analysis of HER2 Receptor Expression In Vivo by Near-Infrared Optical Imaging
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DOI：
10.2310/7290.2010.00018
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发表时间：
2010-07-01
影响因子：
2.8
通讯作者：
Capala, Jacek
中科院分区：
文献类型：
--
作者：
Chernomordik, Victor;Hassan, Moinuddin;Capala, Jacek
人表皮生长因子受体2（HER 2）在乳腺癌中的过度表达与预后不良和对治疗的抵抗有关。目前用于估计这一重要特征的技术使用需要组织活检的离体测定。我们提出了一种新型非侵入性方法，使用光学成像来表征体内HER 2表达，该方法基于HER 2特异性探针（白蛋白结合结构域融合-（Z（HER 2：342））（2）-Cys亲和体分子[Affibody AB，索尔纳，瑞典]，用Alexa Fluor 750标记[分子探针，英杰公司，卡尔斯巴德，加利福尼亚州]），可与HER 2靶向治疗同时使用。皮下肿瘤异种移植物，表达不同水平的HER 2，成像与近红外荧光小动物成像系统在几次注射后的探针。使用房室配体-受体模型从成像数据计算HER 2表达。观察到肿瘤细胞中HER 2扩增/过表达与直接从光学图像序列估计的参数之间的相关性（例如，BT474异种移植物的实验数据表明，表征肿瘤中检测到的荧光强度的时间依赖性的初始斜率线性依赖于HER 2表达，如通过酶联免疫吸附试验对相同肿瘤进行的离体测量）。从表达不同水平HER 2的肿瘤中获得的结果证实了初始斜率和HER 2扩增/过表达之间存在类似的关系。这项工作表明，光学成像，结合数学建模，允许非侵入性监测HER 2在体内的表达。
Human epidermal growth factor receptor 2 (HER2) overexpression in breast cancers is associated with poor prognosis and resistance to therapy. Current techniques for estimating this important characteristic use ex vivo assays that require tissue biopsies. We suggest a novel noninvasive method to characterize HER2 expression in vivo, using optical imaging, based on HER2-specific probes (albumin-binding domain fused-(Z(HER2:342))(2)-Cys Affibody molecules [Affibody AB, Solna, Sweden], labeled with Alexa Fluor 750 [Molecular Probes, Invitrogen, Carlsbad, CA]) that could be used concomitantly with HER2-targeted therapy. Subcutaneous tumor xenografts, expressing different levels of HER2, were imaged with a near-infrared fluorescence small-animal imaging system at several times postinjection of the probe. The compartmental ligand-receptor model was used to calculate HER2 expression from imaging data. Correlation between HER2 amplification/overexpression in tumor cells and parameters, directly estimated from the sequence of optical images, was observed (eg, experimental data for BT474 xenografts indicate that initial slope, characterizing the temporal dependence of the fluorescence intensity detected in the tumor, linearly depends on the HER2 expression, as measured ex vivo by an enzyme-linked immunosorbent assay for the same tumor). The results obtained from tumors expressing different levels of HER2 substantiate a similar relationship between the initial slope and HER2 amplification/overexpression. This work shows that optical imaging, combined with mathematical modeling, allows noninvasive monitoring of HER2 expression in vivo.