Antibody-functionalized nanoparticles for imaging cancer: influence of conjugation to gold nanoparticles on the biodistribution of 89Zr-labeled cetuximab in mice
Antibody-functionalized nanoparticles for imaging cancer: influence of conjugation to gold nanoparticles on the biodistribution of 89Zr-labeled cetuximab in mice
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DOI：
10.1002/cmmi.1539
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发表时间：
2013-09-01
影响因子：
--
通讯作者：
Gallez, Bernard
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文献类型：
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作者：
Karmani, Linda;Labar, Daniel;Gallez, Bernard
抗体标记的金纳米粒子代表了一种有前途的癌症成像和治疗新工具。然而，此类免疫纳米载体的生物分布特征的记录很少。本研究比较了 89Zr 标记的西妥昔单抗与金纳米颗粒 (AuNPs) 偶联反应前后的生物分布，并评估了 89Zr 免疫 PET 的定量成像性能。西妥昔单抗用去铁部分功能化并用 89Zr 标记 (89Zr-Df-Bz-NCS-西妥昔单抗)。根据实验室开发的新方法合成了平均直径为 5 nm 的 AuNP，并使用碳二亚胺化学与 89Zr-Df-Bz-NCS-西妥昔单抗 (AuNPs-PPAA-cetuximab-89Zr) 缀合。将两种示踪剂注射到 A431 异种移植小鼠体内。使用定量 PET 成像在注射后的不同时间评估肿瘤和肝脏的摄取。使用饱和剂量的未标记西妥昔单抗研究了结合的体内特异性。放射性标记的西妥昔单抗与 AuNP 偶联，偶联反应产率 >75%。所有缀合物在体外都是稳定的，在血浆中的稳定程度较低。体内分布研究表明，与未缀合的西妥昔单抗相比，注射后 72 小时内与纳米粒子缀合的西妥昔单抗的肿瘤摄取没有显着差异。免疫 PET 研究表明，AuNPs-PPAA-cetuximab-89Zr 具有较高的肿瘤背景比。与 89Zr-Df-Bz-NCS-cetuximab 相比，AuNPs-PPAA-cetuximab-89Zr 的肝脏摄取更高。体内阻断实验证明偶联反应后选择性肿瘤靶向。这项研究表明，AuNPs 与西妥昔单抗的结合不会影响其肿瘤积累，并且靶向 EGFR 的纳米颗粒的功效没有改变。 89Zr 标记的西妥昔单抗靶向金纳米粒子可能是用于治疗诊断目的的有价值的工具。版权所有 (c) 2013 John Wiley & Sons, Ltd.
Antibody-labeled gold nanoparticles represent a promising novel tool regarding cancer imaging and therapy. Nevertheless, the characterization of biodistribution of such immunonanocarriers has been poorly documented. In this study, the biodistribution of 89Zr-labeled cetuximab before and after the coupling reaction to gold nanoparticles (AuNPs) was compared and the quantitative imaging performance of 89Zr immuno-PET was evaluated. Cetuximab was functionalized with the desferal moiety and labeled with 89Zr (89Zr-Df-Bz-NCS-cetuximab). AuNPs with a mean diameter of 5 nm were synthesized according a new method developed in the laboratory, and conjugated to 89Zr-Df-Bz-NCS-cetuximab using carbodiimide chemistry (AuNPs-PPAA-cetuximab-89Zr). The two tracers were injected in A431 xenograft-bearing mice. Tumor and liver uptakes were assessed at different times after injection using quantitative PET imaging. The in vivo specificity of the binding was investigated using a saturating dose of unlabeled cetuximab. Radiolabeled cetuximab was conjugated to AuNPs with a coupling reaction yield >75%. All conjugates were stablein vitro and to a lesser extent in plasma. In vivo distribution studies revealed no significant difference in tumor uptake for cetuximab conjugated to nanoparticles up to 72 h after injection, compared with unconjugated cetuximab. Immuno-PET studies showed that AuNPs-PPAA-cetuximab-89Zr provided high tumor-to-background ratio. The liver uptake of AuNPs-PPAA-cetuximab-89Zr was higher, compared with 89Zr-Df-Bz-NCS-cetuximab. In vivo blocking experiments demonstrated selective tumor targeting after coupling reaction. This study showed that the conjugation of AuNPs to cetuximab did not affect its tumor accumulation and that the efficacy of EGFR-targeted nanoparticles was unaltered. The 89Zr-labeled cetuximab-targeted gold nanoparticles could be a valuable tool for theranostic purposes. Copyright (c) 2013 John Wiley & Sons, Ltd.