Journal
BIOMATERIALS
Volume 35, Issue 25, Pages 6964-6971Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.04.089
Keywords
Glypican-3; Hepatocellular carcinoma; Immuno-PET; Zr-89; Molecular imaging
Funding
- T.S. Kwok Liver Research Foundation
- C.J. Huang Foundation
- Stanford Cancer Center (DCRA)
Ask authors/readers for more resources
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 Zr-89-DFO-1G12 by bioconjugating and radiolabeling the anti-GPC3 monoclonal antibody (clone 1G12) with Zr-89, and evaluated its tumor-targeting capacity. In vitro, Zr-89-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, Zr-89-DFO-1G12 specifically accumulated in subcutaneous GPC3-positive HCC xenografts only, but not in PC3 xenografts. Importantly, Zr-89-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, Zr-89-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. (C) 2014 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available