Nanographene oxide-based radioimmunoconstructs for in vivo targeting and SPECT imaging of HER2-positive tumors
Nanographene oxide-based radioimmunoconstructs for in vivo targeting and SPECT imaging of HER2-positive tumors
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DOI：
10.1016/j.biomaterials.2012.10.054
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发表时间：
2013-01-01
期刊：
影响因子：
14
通讯作者：
Vallis, Katherine A.
中科院分区：
文献类型：
--
作者：
Cornelissen, Bart;Able, Sarah;Vallis, Katherine A.
纳米氧化石墨烯（NGO）是一种新型的纳米壁材料，可以在体内追踪肿瘤，并且由于其大的表面积，具有携带大有效载荷的能力。本研究探讨了使用抗HER 2抗体（曲妥珠单抗）结合的非政府组织，放射性标记的In-111-苄基-二亚乙基三胺五乙酸（BnDTPA）通过π π堆积，功能成像。在两种HER 2过表达的人乳腺癌小鼠模型中，实现了高肿瘤-肌肉比，从而使用单光子发射计算机断层扫描（SPECT）清晰地显示肿瘤。在BALB/neuT模型和携带231/H2 N异种移植物的BALB/c nu/nu小鼠中，72 h时肿瘤蓄积量分别为注射剂量/g（%ID/g）肿瘤组织的12.7 +/- 0.67和15.0 +/- 3.7%，肿瘤-肌肉比分别为35：1和7：1。放射性标记的NGO-曲妥珠单抗偶联物显示出比不含NGO的放射性标记的曲妥珠单抗更好的上级药代动力学，从循环中清除更快。使用非政府组织作为支架来构建放射性标记的纳米免疫构建物为肿瘤的分子成像带来了希望。(C)2012爱思唯尔有限公司保留所有权利。
Nanographene oxide (NGO) is a novel nano-wall material that tracks to tumors in vivo, and which, as a consequence of its large surface area, has the capacity to carry a large payload. This study explores the use of anti-HER2 antibody (trastuzumab)-conjugated NGO, radiolabeled with In-111-benzyl-diethylene-triaminepentaacetic acid (BnDTPA) via pi pi-stacking, for functional imaging. In two HER2-overexpressing murine models of human breast cancer, high tumor-to-muscle ratio was achieved, resulting in clear visualization of tumor using single-photon emission computed tomography (SPECT). In the BALB/neuT model and in BALB/c nu/nu mice bearing 231/H2N xenografts, tumor accumulation amounted to 12.7 +/- 0.67 and 15.0 +/- 3.7% of the injected dose/g (%ID/g) of tumor tissue at 72 h, with tumor-to-muscle ratios of 35:1 and 7:1, respectively. Radiolabeled NGO-trastuzumab conjugates demonstrated superior pharmacokinetics compared to radiolabeled trastuzumab without NGO, with more rapid clearance from the circulation. The use of NGO as a scaffold to build radiolabeled nano-immunoconstructs holds promise for molecular imaging of tumors. (C) 2012 Elsevier Ltd. All rights reserved.