Development and evaluation of a cetuximab-based imaging probe to target EGFR and EGFRvIII
Development and evaluation of a cetuximab-based imaging probe to target EGFR and EGFRvIII
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DOI：
10.1016/j.radonc.2007.04.030
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发表时间：
2007-06-01
影响因子：
5.7
通讯作者：
Lambin, Philippe
中科院分区：
文献类型：
--
作者：
Aerts, Hugo J. W. L.;Dubois, Ludwig;Lambin, Philippe
背景和目的：表皮生长因子受体（EGFR）在很大比例的人类恶性肿瘤中过度表达，其表达与肿瘤侵袭性和治疗耐药性相关。单克隆抗体西妥昔单抗 (IMC-C225) 以高亲和力阻断 EGFIR 的配体结合域，阻止下游信号传导，从而抑制肿瘤生长。我们使用 Oregon Green 488 [改进的西妥昔单抗]开发并表征了一种新型成像探针，以评估其作为靶向 EGFR 的成像剂的用途。材料和方法：使用具有不同表达水平的 EGFR 或 EGFR 突变形式（称为 EGFRvIII）的细胞进行体外验证。标记的西妥昔单抗与 EGFR 的体内结合也在离体肿瘤材料上进行了评估。结果：俄勒冈绿 488 标记的西妥昔单抗的开发是成功的，证明了在体外与 EGFR 和 EGFRvIII 的结合。体内也发现了蓄积，并通过使用抗 EGFR 抗体的组织病理学证实了这一点。然而，显着的不匹配凸显了体内药物递送和 EGFR 细胞表达水平之间的差异。结论：单克隆抗体西妥昔单抗代表了一种有前途的探针，可用于评估体内西妥昔单抗与 EGFR 结合的生物学和药代动力学效应。它不仅可以显示野生型 EGFR 的存在，还可以显示突变型 EGFRvIII 的存在。 (C) 2007 Elsevier Ireland Ltd. 保留所有权利。
Background and purpose: The epidermal growth factor receptor (EGFR) is overexpressed in a significant percentage of human malignancies and its expression is associated with tumour aggressiveness and treatment resistance. The monoclonal antibody cetuximab (IMC-C225) blocks the hgand-binding domain of EGFIR with high affinity, preventing downstream signalling resulting in tumour growth inhibition. We developed and characterized a novel imaging probe using Oregon Green 488 [abetted cetuximab to evaluate its usage as an imaging agent to target EGFR.Materials and methods: Cells with varying expression levels of EGFR or a mutant form of EGFR, called EGFRvIII, were used for in vitro validation. The in vivo binding of labelled cetuximab to EGFR was also assessed ex vivo on tumour material.Results: The development of Oregon Green 488 labelled cetuximab was successful, demonstrating binding to both EGFR and EGFRvIII in vitro. Accumulation was also found in vivo, which was confirmed by histopathology using anti-EGFR antibodies. However, significant mismatch highlights differences between drug delivery in vivo, and cell expression levels of EGFR.Conclusions: The monoclonal antibody cetuximab represents a promising probe to evaluate the biologic and pharmacokinetic effects of in vivo cetuximab binding to EGFR. It not only visualizes the presence of the wild type EGFR, but also the presence of the mutant EGFRvIII. (C) 2007 Elsevier Ireland Ltd. All rights reserved.