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Glypican-3-targeted 89Zr PET imaging of hepatocellular carcinoma.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine (2014-03-15)
Jonathan G Sham, Forrest M Kievit, John R Grierson, Robert S Miyaoka, Matthew M Yeh, Miqin Zhang, Raymond S Yeung, Satoshi Minoshima, James O Park
ABSTRACT

Hepatocellular carcinoma (HCC) is a devastating malignancy in which imperfect imaging plays a primary role in diagnosis. Glypican-3 (GPC3) is an HCC-specific cell surface proteoglycan overexpressed in most HCCs. This paper presents the use of (89)Zr-conjugated monoclonal antibody against GPC3 ((89)Zr-αGPC3) for intrahepatic tumor localization using PET. Polymerase chain reaction confirmed relative GPC3 expression in cell lines. In vitro binding, in vivo biodistribution, and small-animal PET studies were performed on GPC3-expressing HepG2 and non-GPC3-expressing HLF and RH7777 cells and orthotopic xenografts. (89)Zr-αGPC3 demonstrated antibody-dependent, antigen-specific tumor binding. HepG2 liver tumors exhibited high peak uptake (836.6 ± 86.6 percentage injected dose [%ID]/g) compared with background liver (27.5 ± 1.6 %ID/g). Tumor-to-liver contrast ratio was high and peaked at 32.5. The smallest HepG2 tumor (<1 mm) showed lower peak uptake (42.5 ± 6.4 %ID/g) and tumor-to-liver contrast (1.57) but was still clearly visible on PET. Day 7 tissue activity was still substantial in HepG2 tumors (466.4 ± 87.6 %ID/g) compared with control RH7777 tumors (3.9 ± 1.3 %ID/g, P < 0.01), indicating antigen specificity by (89)Zr-αGPC3. HepG2 tumor treated with unlabeled αGPC3 or heat-denatured (89)Zr-αGPC3 demonstrated tumor activity (2.1 %ID/g) comparable to that of control xenografts, confirming antibody dependency. This study demonstrated the feasibility of using (89)Zr-αGPC3 to image HCC in the liver, as well as the qualitative determination of GPC3 expression via small-animal PET. The ability to clarify the identity of small liver lesions with an HCC-specific PET probe would provide clinicians with vital information that could significantly alter patient management, warranting further investigation for clinical translation.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Collagen from bovine nasal septum, Bornstein and Traub Type II, powder
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Zirconium, powder, −100 mesh
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Zirconium, rod, diam. 6.35 mm, ≥99% trace metals basis
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Collagen from calf skin, Bornstein and Traub Type I, (0.1% solution in 0.1 M acetic acid), aseptically processed, BioReagent, suitable for cell culture
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Zirconium, foil, light tested, 100x100mm, thickness 0.05mm, annealed, 99.2%
Zirconium, foil, 8mm disks, thickness 0.075mm, annealed, 99.2%
Zirconium, foil, light tested, 100x100mm, thickness 0.008mm, 99.2%
Zirconium, foil, 25mm disks, thickness 0.5mm, annealed, 99.2%
Zirconium, foil, 8mm disks, thickness 0.5mm, annealed, 99.2%
Zirconium, foil, 4mm disks, thickness 0.01mm, 99.2%
Zirconium, foil, light tested, 100x100mm, thickness 0.01mm, 99.2%
Zirconium, foil, 8mm disks, thickness 0.02mm, 99.2%
Zirconium, foil, 6mm disks, thickness 0.01mm, 99.2%
Zirconium, foil, 2m coil, thickness 0.075mm, annealed, 99.2%
Zirconium, foil, 25mm disks, thickness 0.25mm, annealed, 99.2%
Zirconium, foil, light tested, 100x100mm, thickness 0.009mm, 99.2%
Zirconium, foil, 4mm disks, thickness 0.0125mm, 99.2%
Zirconium, foil, 6mm disks, thickness 0.5mm, annealed, 99.2%
Zirconium, foil, 5m coil, thickness 0.025mm, annealed, 99.2%
Zirconium, foil, 4mm disks, thickness 0.25mm, annealed, 99.2%
Zirconium, foil, 8mm disks, thickness 0.05mm, annealed, 99.2%
Zirconium, foil, 50mm disks, thickness 0.025mm, annealed, 99.2%
Zirconium, foil, 4mm disks, thickness 0.01mm, 99.2%
Zirconium, foil, light tested, 100x100mm, thickness 0.0125mm, 99.2%