In vivo diagnosis of epidermal growth factor receptor expression using molecular imaging with a cocktail of optically labeled monoclonal antibodies
In vivo diagnosis of epidermal growth factor receptor expression using molecular imaging with a cocktail of optically labeled monoclonal antibodies
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DOI：
10.1158/1078-0432.ccr-07-1119
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发表时间：
2007-11-15
影响因子：
11.5
通讯作者：
Kobayashi, Hisataka
中科院分区：
文献类型：
--
作者：
Barrett, Tristan;Koyama, Yoshinori;Kobayashi, Hisataka
目的：表皮生长因子受体（EGFR）在肿瘤发生中起重要作用，因此已成为新型分子疗法的靶点。在此，我们使用一种针对EGFR - 1（HER1）和EGFR - 2（HER2）的光学标记单克隆抗体“鸡尾酒”，通过细胞表面表达谱来区分肿瘤。
实验设计：在荷瘤小鼠皮下注射A431（HER1过表达）、NIH3T3/HER2 +（HER2过表达）和Balb3T3/DsRed（不表达对照）细胞系后进行体内成像实验。肿瘤形成后，将一种光学标记抗体的混合物：Cy5.5标记的西妥昔单抗（抗HER1）和Cy7标记的曲妥珠单抗（抗HER2）静脉注射。进行体内和体外荧光成像。为了与放射性核素成像进行比较，使用(111)铟标记的抗体进行实验。此外，对患有一种肿瘤类型的小鼠进行了“盲法”诊断研究。
结果：对患有三种肿瘤类型的14只小鼠进行的体内光谱荧光分子成像，使用光学标记抗体混合物在体内和体外都能清楚地区分肿瘤。注射后24小时，A431和NIH3T3/HER2 +肿瘤分别通过Cy5.5和Cy7光谱图像上的峰值被明显检测到；放射性核素成像在这个时间点无法清楚地区分肿瘤。在盲法单肿瘤实验中，研究人员能够正确诊断出总共40个肿瘤。
结论：一种使用抗体混合物的体内成像技术可同时区分两种表达不同EGFR的肿瘤，并能对每种亚型进行准确表征。
Purpose: Epidermal growth factor receptors (EGFR) play an important role in tumorigenesis and, therefore, have become targets for new molecular therapies. Here, we use a '' cocktail '' of optically labeled monoclonal antibodies directed against EGFR-1 (HER1) and EGFR-2 (HER2) to distinguish tumors by their cell surface expression profiles. Experimental Design: In vivo imaging experiments were done in tumor-bearing mice following s.c. injection of A431 (overexpressing HER1), NIH3T3/HER2+ (overexpressing HER2), and Balb3T3/DsRed (non-expression control) cell lines. After tumor establishment, a cocktail of optically labeled antibodies: Cy5.5-labeled cetuximab (anti-HER1) and Cy7-labeled trastuzumab (anti-HER2) was i.v. injected. In vivo and ex vivo fluorescence imaging was done. For comparison with radionuclide imaging, experiments were undertaken using (111)Indium-labeled antibodies. Additionally, a '' blinded '' diagnostic study was done for mice bearing one tumor type. Results: In vivo spectral fluorescent molecular imaging of 14 mice with three tumor types clearly differentiated tumors using the cocktail of optically labeled antibodies both in vivo and ex vivo. Twenty-four hours after injection, A431 and NIH3T3/HER2+ tumors were detected distinctly by their peak on Cy5.5 and Cy7 spectral images, respectively; radionuclide imaging was unable to clearly distinguish tumors at this time point. In blinded single tumor experiments, investigators were able to correctly diagnose a total of 40 tumors. Conclusion: An in vivo imaging technique using an antibody cocktail simultaneously differentiated two tumors expressing distinct EGFRs and enabled an accurate characterization of each subtype.