Near infrared fluorescence imaging of EGFR expression in vivo using IRDye800CW-nimotuzumab.
Near infrared fluorescence imaging of EGFR expression in vivo using IRDye800CW-nimotuzumab.
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DOI：
10.18632/oncotarget.23557
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发表时间：
2018-01-19
期刊：
影响因子：
--
通讯作者：
Geyer CR
中科院分区：
文献类型：
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作者：
Bernhard W;El-Sayed A;Barreto K;Gonzalez C;Hill W;Parada AC;Fonge H;Geyer CR
尼妥珠单抗是一种人源化抗表皮生长因子受体（EGFR）单克隆抗体，在许多国家获批用于治疗EGFR阳性癌症。近红外（NIR）荧光染料标记的抗体代表一类有吸引力的图像引导手术探针，因为它们具有高特异性、肿瘤摄取和与表达抗原的肿瘤细胞的低解离。在这项研究中，我们开发了一种近红外荧光染料标记的尼妥珠单抗免疫偶联物，IRDye 800 CW-尼妥珠单抗，并评估了与EGFR阳性细胞的体外结合，通过近红外荧光成像的体内肿瘤摄取和离体生物分布。尼妥珠单抗和IRDye 800 CW-尼妥珠单抗与EGFR阳性细胞的结合没有差异。在携带EGFR阳性异种移植物的小鼠中，IRDye 800 CW-尼妥珠单抗摄取在注射后4天达到峰值，此后缓慢下降，在注射后28天仍观察到高水平的蓄积。在EGFR阳性异种移植物中，与IRDye 800 CW-西妥昔单抗相比，IRDye 800 CW-尼妥珠单抗在肿瘤中的摄取高出2倍以上。此外，IRDye 800 CW-尼妥珠单抗的肝脏摄取比西妥昔单抗低两倍。IRDye 800 CW-尼妥珠单抗的较低肝脏摄取可能对免疫缀合物的临床试验的选择剂量具有影响。总之，这项研究表明，尼妥珠单抗是NIR荧光成像和图像引导手术的良好候选者。
Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody that is approved in many countries for the treatment of EGFR-positive cancers. Near infrared (NIR) fluorescent dye-labeled antibodies represent an attractive class of image-guided surgical probes because of their high specificity, tumor uptake, and low dissociation from tumor cells that express the antigen. In this study, we developed a NIR fluorescent dye-labeled nimotuzumab immunoconjugate, IRDye800CW-nimotuzumab, and evaluated in vitro binding with EGFR-positive cells, in vivo tumor uptake by NIR fluorescent imaging, and ex vivo biodistribution. There was no difference in binding between nimotuzumab and IRDye800CW-nimotuzumab to EGFR-positive cells. In mice bearing EGFR-positive xenografts, IRDye800CW-nimotuzumab uptake peaked at 4 days post injection and slowly decreased thereafter with high levels of accumulation still observed at 28 days post injection. In EGFR-positive xenografts, IRDye800CW-nimotuzumab showed more than 2-fold higher uptake in tumors compared to IRDye800CW-cetuximab. In addition, liver uptake of IRDye800CW-nimotuzumab was two-fold lower than cetuximab. The lower liver uptake of IRDye800CW-nimotuzumab could have implications on the selected dose for clinical trials of the immunoconjugate. In summary, this study shows that nimotuzumab is a good candidate for NIR fluorescent imaging and image-guided surgery.