Research ArticleBasic Science Investigations

In Vivo Visualization of MET Tumor Expression and Anticalin Biodistribution with the MET-Specific Anticalin 89Zr-PRS-110 PET Tracer

Anton G.T. Terwisscha van Scheltinga, Marjolijn N. Lub-de Hooge, Marlon J. Hinner, Remy B. Verheijen, Andrea Allersdorfer, Martin Hülsmeyer, Wouter B. Nagengast, Carolien P. Schröder, Jos G.W. Kosterink, Elisabeth G.E. de Vries, Laurent Audoly and Shane A. Olwill
Journal of Nuclear Medicine April 2014, 55 (4) 665-671; DOI: https://doi.org/10.2967/jnumed.113.124941

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Figures

  • FIGURE 1.
    FIGURE 1.

    Membrane binding and internalization of 89Zr-PRS-110 after binding MET on H441 cells. Cell surface (acid buffer), intracellular, and supernatant fraction radioactivity, expressed as percentage of total activity. Data were obtained in 3 independent experiments.

  • FIGURE 2.
    FIGURE 2.

    Biodistribution of 89Zr-PRS-110 at 96 h as determined by ex vivo analysis. Four dose groups of 10, 50, 100, and 500 μg of PRS-110 (with 10 μg of 89Zr-PRS-110 per group) were included in dose-escalation biodistribution in H441 human tumor–bearing mice (4–6 mice per group). Data are expressed as %ID/g.

  • FIGURE 3.
    FIGURE 3.

    Ex vivo tumor analysis of PRS-110 distribution 96 h after tracer injection in H441 tumor visualized by fluorescence microscopy. Green is from IRDye 800CW conjugated to PRS-110, and nuclei (in red) are visualized. In background, tumor structure is visible. MET status of H441, U87-MG, and A2780 was determined by immunohistochemistry, and representative picture is included.

  • FIGURE 4.
    FIGURE 4.

    89Zr-PRS-110 small-animal PET imaging of H441-bearing mice. (A) Representative transversal and coronal small-animal PET images are shown at 6, 24, 48, and 96 h after tracer injection. (B) Small-animal PET data quantification was performed for blood pool, liver, spleen, kidney, and tumor uptake in all mice (4–6 mice per group). Data are expressed as mean standardized uptake value (SUVmean).

  • FIGURE 5.
    FIGURE 5.

    89Zr-PRS-110 small-animal PET imaging of H441- (A), U87-MG- (B), and A2780-bearing mice (C). Representative transversal and coronal small-animal PET images are shown in the upper panel at 96 h after tracer injection of 89Zr-PRS-110 for MET-driven tumor uptake and 89Zr-Tlc-PEG for nonspecific tumor uptake. Ex vivo tumor uptake of 89Zr-PRS-110 and 89Zr-Tlc-PEG is shown in the lower panel. To compare specific tumor uptake between tumor models, tumor-to-blood ratios are provided (4–6 mice per group).

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