Research ArticleBasic Science Investigations

Glypican-3–Targeted 89Zr PET Imaging of Hepatocellular Carcinoma

Jonathan G. Sham, Forrest M. Kievit, John R. Grierson, Robert S. Miyaoka, Matthew M. Yeh, Miqin Zhang, Raymond S. Yeung, Satoshi Minoshima and James O. Park
Journal of Nuclear Medicine May 2014, 55 (5) 799-804; DOI: https://doi.org/10.2967/jnumed.113.132118

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Quantitative real-time polymerase chain reaction data demonstrating GPC3 expression relative to GAPDH across multiple cell lines verified by 2 nonoverlapping primer pairs.

  • FIGURE 2.
    FIGURE 2.

    In vitro binding of 89Zr-αGPC3 after 1 h of treatment. All results are in HepG2 cells except final column (HLF).

  • FIGURE 3.
    FIGURE 3.

    Tissue biodistribution measured by Cobra II γ counter in non–tumor-bearing 8-wk-old female Nu/J mice (n = 4 each). Blocking was performed with 1.0–1.2 mg of unlabeled αGPC3.

  • FIGURE 4.
    FIGURE 4.

    (A) IVIS luminescent images before administration of 89Zr-αGPC3. (B) Selected small-animal PET images of same animals showing tumor concordance in HepG2 tumor-bearing animals and lack of tumor uptake in RH7777, blocked, and heat-denatured controls. Signal saturation was permitted to enable comparisons between animals. Blue arrowheads indicate tumor location; red arrow indicates spleen. (C) Day 7 decay-corrected biodistribution of 89Zr-αGPC3 confirming low liver tumor uptake in RH7777, blocked, and heat-denatured controls.

  • FIGURE 5.
    FIGURE 5.

    (A and B) Serial decay-corrected whole-body small-animal PET images of mouse bearing large HepG2 tumor (3.8 mm) (A) and small HepG2 tumor (<1 mm) (B). Blue arrowhead indicates tumor location. (C and D) Average tumor and liver activity obtained from small-animal PET data for mouse with large HepG2 tumor (C) and mouse with small HepG2 tumor (D).

  • FIGURE 6.
    FIGURE 6.

    Histologic sections of PET-imaged mouse liver (L) and liver tumor (T) stained with hematoxylin and eosin (top row) and immunohistochemistry against GPC3 (middle row) viewed at ×100 magnification. Immunohistochemistry confirms polymerase chain reaction data showing high expression in HepG2 and minimal expression in RH7777 tumors. Bottom row demonstrates immunofluorescence of goat antimouse secondary antibody binding against mouse antihuman αGPC3 in HepG2 and RH7777 tumors.

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