Rapid Visualization of Human Tumor Xenografts through Optical Imaging with a Near-infrared Fluorescent Anti-Epidermal Growth Factor Receptor Nanobody
Rapid Visualization of Human Tumor Xenografts through Optical Imaging with a Near-infrared Fluorescent Anti-Epidermal Growth Factor Receptor Nanobody
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DOI：
10.2310/7290.2011.00025
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发表时间：
2012-01-01
影响因子：
2.8
通讯作者：
van Bergen en Henegouwen, Paul M. P.
中科院分区：
文献类型：
--
作者：
Oliveira, Sabrina;van Dongen, Guus A. M. S.;van Bergen en Henegouwen, Paul M. P.
鉴于表皮生长因子受体（EGFR）的过度表达被发现在许多类型的人类上皮癌，这种受体的非侵入性分子成像是极大的兴趣。许多研究采用单克隆抗体作为探针;然而，它们在血流中的特征性长半衰期鼓励了更小探针的开发。在这项研究中，开发了一种基于抗EGFR纳米抗体的探针，并与西妥昔单抗进行了比较，以应用于光学分子成像。为此，将抗EGFR纳米抗体7 D12和西妥昔单抗缀合至近红外荧光团IRDye 800 CW。7 D12-IR允许肿瘤早在注射后30分钟可视化，而西妥昔单抗-IR在肿瘤部位没有观察到高于背景的信号。注射7 D12-IR后2小时，肿瘤中IR结合蛋白的定量显示约为注射剂量的17%/g，这显著高于注射西妥昔单抗-IR后24小时获得的肿瘤摄取。这些结果表明，这种与NIR荧光团缀合的抗EGFR纳米抗体具有用于快速临床前光学成像的优异特性，这有望在未来用作人类的补充诊断工具。
Given that overexpression of the epidermal growth factor receptor (EGFR) is found in many types of human epithelial cancers, noninvasive molecular imaging of this receptor is of great interest. A number of studies have employed monoclonal antibodies as probes; however, their characteristic long half-life in the bloodstream has encouraged the development of smaller probes. In this study, an anti-EGFR nanobody-based probe was developed and tested in comparison with cetuximab for application in optical molecular imaging. To this aim, the anti-EGFR nanobody 7D12 and cetuximab were conjugated to the near-infrared fluorophore IRDye800CW. 7D12-IR allowed the visualization of tumors as early as 30 minutes postinjection, whereas with cetuximab-IR, no signal above background was observed at the tumor site. Quantification of the IR-conjugated proteins in the tumors revealed approximate to 17% of injected dose per gram 2 hours after injection of 7D12-IR, which was significantly higher than the tumor uptake obtained 24 hours after injection of cetuximab-IR. This difference is associated with the superior penetration and distribution of 7D12-IR within the tumor. These results demonstrate that this anti-EGFR nanobody conjugated to the NIR fluorophore has excellent properties for rapid preclinical optical imaging, which holds promise for its future use as a complementary diagnostic tool in humans.