In vivo diagnosis of epidermal growth factor receptor expression using molecular imaging with a cocktail of optically labeled monoclonal antibodies

被引:86
作者
Barrett, Tristan
Koyama, Yoshinori
Hama, Yukihiro
Ravizzini, Gregory
Shin, In Soo
Jang, Beom-Su
Paik, Chang H.
Urano, Yasuteru
Choyke, Peter L.
Kobayashi, Hisataka
机构
[1] Ctr Canc Res, Natl Canc Inst, Mol Imaging Program, Bethesda, MD USA
[2] NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA
[3] Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo, Japan
关键词
D O I
10.1158/1078-0432.CCR-07-1119
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页码:6639 / 6648
页数:10
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