Biomaterials xxx (2014) 1e8

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Imaging of hepatocellular carcinoma patient-derived xenografts using 89 Zr-labeled anti-glypican-3 monoclonal antibody Xiaoyang Yang a, Hongguang Liu b, Chris K. Sun a, Arutselvan Natarajan b, Xiang Hu b, Xiaolin Wang a, Mark Allegretta c, Ronald D. Guttmann c, Sanjiv S. Gambhir b, Mei-Sze Chua a, *, Zhen Cheng b, **, Samuel K. So a a b c

Asian Liver Center, Department of Surgery, Stanford University, School of Medicine, Stanford, CA 94305, USA Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University, Stanford, CA 94305, USA BioMosaics, Inc., Burlington, VT 05405, USA

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a b s t r a c t

Article history: Received 24 March 2014 Accepted 19 April 2014 Available online xxx

Imaging probes for early detection of hepatocellular carcinoma (HCC) are highly desired to overcome current diagnostic limitations which lead to poor prognosis. The membrane protein glypican-3 (GPC3) is a potential molecular target for early HCC detection as it is over-expressed in >50% of HCCs, and is associated with early hepatocarcinogenesis. We synthesized the positron emission tomography (PET) probe 89Zr-DFO-1G12 by bioconjugating and radiolabeling the anti-GPC3 monoclonal antibody (clone 1G12) with 89Zr, and evaluated its tumor-targeting capacity. In vitro, 89Zr-DFO-1G12 was specifically taken up into GPC3-positive HCC cells only, but not in the GPC3-negative prostate cancer cell line (PC3). In vivo, 89Zr-DFO-1G12 specifically accumulated in subcutaneous GPC3-positive HCC xenografts only, but not in PC3 xenografts. Importantly, 89Zr-DFO-1G12 delineated orthotopic HCC xenografts from surrounding normal liver, with tumor/liver (T/L) ratios of 6.65  1.33 for HepG2, and 4.29  0.52 for Hep3B xenografts. It also delineated orthotopic xenografts derived from three GPC3-positive HCC patient specimens, with T/L ratios of 4.21  0.64, 2.78  0.26, and 2.31  0.38 at 168 h p.i. Thus, 89Zr-DFO-1G12 is a highly translatable probe for the specific and high contrast imaging of GPC3-positive HCCs, which may aid early detection of HCC to allow timely intervention. Ó 2014 Elsevier Ltd. All rights reserved.

Keywords: Glypican-3 Hepatocellular carcinoma Immuno-PET 89 Zr Molecular imaging

1. Introduction Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide [1e3]. Early detection of HCC is crucial and may significantly improve its outcome, since its typically late diagnosis is associated with limited treatment options and lower chances of survival [4e6]. Current diagnostic imaging of HCC based on ultrasonography, computed tomography, and magnetic resonance imaging [7] is limited as they are often incapable of detecting HCC lesions

Imaging of hepatocellular carcinoma patient-derived xenografts using ⁸⁹Zr-labeled anti-glypican-3 monoclonal antibody.

Imaging probes for early detection of hepatocellular carcinoma (HCC) are highly desired to overcome current diagnostic limitations which lead to poor ...
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