Research ArticleBasic Science Investigations

Quantitative PET of Human Urokinase-Type Plasminogen Activator Receptor with 64Cu-DOTA-AE105: Implications for Visualizing Cancer Invasion

Morten Persson, Jacob Madsen, Søren Østergaard, Mette Munk Jensen, Jesper Tranekjær Jørgensen, Karina Juhl, Charlotte Lehmann, Michael Ploug and Andreas Kjaer
Journal of Nuclear Medicine January 2012, 53 (1) 138-145; DOI: https://doi.org/10.2967/jnumed.110.083386

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Chemical structures of DOTA-AE105 (A) and control peptide inactive DOTA-AE105 (B), in which 2 essential amino acids for uPAR binding (Phe → Glu and Trp → Glu) are substituted.

  • FIGURE 2.
    FIGURE 2.

    Biodistribution results for 64Cu-DOTA-AE105 and inactive 64Cu-DOTA-AE105 in nude mice bearing subcutaneously xenotransplanted U87MG human glioblastoma at 4.5 h after injection. Results are shown as %ID/g ± SEM (n = 3 mice/group).

  • FIGURE 3.
    FIGURE 3.

    Representative decay-corrected transverse images at 4.5 h after injection of 64Cu-DOTA-AE105, inactive 64Cu-DOTA-AE105, and 64Cu-DOTA-AE105 preinjected with excess of DOTA-AE105 (blocking) (A). Representative images shown are static scans of single mouse (arrows indicate tumors), which is representative of 3 mice tested in each group, with corresponding quantitative tumor ROI analysis (B). Results are shown as %ID/g ± SEM (n = 3 mice/group).

  • FIGURE 4.
    FIGURE 4.

    Decay-corrected transverse images of subcutaneously xenotransplanted U87MG, HT-29, and H727 mice at 1, 4.5, and 22 h after injection of 64Cu-DOTA-AE105 (A). Images shown are static scans of single mouse, which is representative of 4 mice tested in each group. Arrows indicate tumors. Correlation between tumor uptake at 1 h after injection of 64Cu-DOTA-AE105 (%ID/g) and corresponding uPAR expression (pg/mg) is depicted (n = 16 tumors) (B).

  • FIGURE 5.
    FIGURE 5.

    Representative decay-corrected coronal (top) and transversal (bottom) images of same mouse at 1 h after injection of either 18F-FDG or 64Cu-DOTA-AE105 (A). Mouse was inoculated with 2 different xenotransplanted tumors on each flank (H727 and U87MG). Arrows indicate tumor. Comparison of quantified tumor uptake of 18F-FDG and 64Cu-DOTA-AE105 in 3 combination mice bearing two different human cancer xenografts (combi-mice) is shown. Results are shown as %ID/g ± SEM (n = 3) (B).

  • FIGURE 6.
    FIGURE 6.

    High-resolution uPAR PET images of tumor and corresponding immunohistologic slides for HT-29 (A, C, and E) and U87MG (B, D, and F). One tumor for each type was PET-scanned and afterward resected and stained for human uPAR. High degree of correlation between uPAR expression pattern and uptake of 64Cu-DOTA-AE105 in each tumor was observed. Bar = 1 mm in A–D and 40 μm in E–F.

  • FIGURE 7.
    FIGURE 7.

    Correlation between baseline uPAR expression levels detected by 64Cu-DOTA-AE105 PET at day 0 and sensitivity toward 5-fluorouracil chemotherapy treatment (P = 0.05, r2 = 0.32) in nude mice bearing human colorectal HT-29 cancer xenografts (n = 12 tumors).

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