Journal
BIOMATERIALS
Volume 34, Issue 4, Pages 1146-1154Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.10.054
Keywords
Nanographene oxide; (111)Indium; Molecular imaging; Trastuzumab; SPECT
Funding
- CR-UK/EPSRC/MRC/NIHR Oxford Cancer Imaging Centre
- NIHR Oxford Biomedical Research Centre
- Cancer Research-UK
- Cancer Research UK [16466, 11564] Funding Source: researchfish
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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.
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