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 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 (89)Zr-DFO-1G12 by bioconjugating and radiolabeling the anti-GPC3 monoclonal antibody (clone 1G12) with (89)Zr, and evaluated its tumor-targeting capacity. In vitro, (89)Zr-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, (89)Zr-DFO-1G12 specifically accumulated in subcutaneous GPC3-positive HCC xenografts only, but not in PC3 xenografts. Importantly, (89)Zr-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, (89)Zr-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.
Asian Liver Center, Department of Surgery, Stanford University, School of Medicine, Stanford, CA 94305, USA.
Xiaoyang
X
Yang
Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University, Stanford, CA 94305, USA.
Hongguang
H
Liu
Asian Liver Center, Department of Surgery, Stanford University, School of Medicine, Stanford, CA 94305, USA.
Chris K
CK
Sun
Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University, Stanford, CA 94305, USA.
Arutselvan
A
Natarajan
Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University, Stanford, CA 94305, USA.
Xiang
X
Hu
Asian Liver Center, Department of Surgery, Stanford University, School of Medicine, Stanford, CA 94305, USA.
Xiaolin
X
Wang
BioMosaics, Inc., Burlington, VT 05405, USA.
Mark
M
Allegretta
BioMosaics, Inc., Burlington, VT 05405, USA.
Ronald D
RD
Guttmann
Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University, Stanford, CA 94305, USA.
Sanjiv S
SS
Gambhir
Asian Liver Center, Department of Surgery, Stanford University, School of Medicine, Stanford, CA 94305, USA. Electronic address: mchua@stanford.edu.
Mei-Sze
MS
Chua
Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University, Stanford, CA 94305, USA. Electronic address: zcheng@stanford.edu.
Zhen
Z
Cheng
Asian Liver Center, Department of Surgery, Stanford University, School of Medicine, Stanford, CA 94305, USA.
Samuel K
SK
So
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000473:pathology; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D053673:Glypicans / Q000737:chemistry; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D049268:Positron-Emission Tomography; D015040:Zirconium / Q000737:chemistry
D000911:Antibodies, Monoclonal; D053673:Glypicans; D015040:Zirconium
(89)Zr; Glypican-3; Hepatocellular carcinoma; Immuno-PET; Molecular imaging