Research ArticleBasic Science Investigations

A Tyrosine Kinase Inhibitor–Based High-Affinity PET Radiopharmaceutical Targets Vascular Endothelial Growth Factor Receptor

Feng Li, Sheng Jiang, Youli Zu, Daniel Y. Lee and Zheng Li
Journal of Nuclear Medicine September 2014, 55 (9) 1525-1531; DOI: https://doi.org/10.2967/jnumed.114.138925

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Chemical structures of ZD6474 (ZD-G1), ZD-G2, 64Cu-DOTA-ZD-G1, and 64Cu-DOTA-ZD-G2.

  • FIGURE 2.
    FIGURE 2.

    Cell uptake and competition assay. (A) Binding of 64Cu-DOTA-ZD-G2 to cells with varying levels of VEGFR2. (B) Comparison of cell binding with 64Cu-DOTA-ZD-G2 and 64Cu-DOTA-ZD-G1 in U-87 cells. Competitive blocking with nonradioactive ZD-G2 and ZD-G1, respectively. (n = 3, **P < 0.0001).

  • FIGURE 3.
    FIGURE 3.

    Characterization of VEGFR2-specific binding. (A) Saturation curve of 64Cu-DOTA-ZD-G1 bound to U-87 cells (Kd, 44.75 ± 15.04 nM). (B) Saturation curve of 64Cu-DOTA-ZD-G2 bound to U-87 cells. (Kd, 0.45 ± 0.32 nM. (C) Competition-binding curve of 64Cu-DOTA-ZD-G2 and 64Cu-DOTA-ZD-G1 to U-87 cells. Log of concentration of competitor compounds versus percentage of maximum specific binding of radiolabeled molecules.

  • FIGURE 4.
    FIGURE 4.

    Small-animal PET/CT imaging of U-87 tumor–bearing mice. Serial small-animal PET/CT scans of U-87 tumor–bearing mice injected intravenously with approximately 3.7 MBq of 64Cu-DOTA-ZD-G1 (A) and 64Cu-DOTA-ZD-G2 (B). Tumors are indicated by arrowheads.

  • FIGURE 5.
    FIGURE 5.

    Representative whole-body PET/CT images of U-87 MG tumor–bearing mice at 24 h after injection of 64Cu-DOTA-ZD-G2 (left) and 64Cu-DOTA-ZD-G2 coinjected with 60 μg of ZD-G2 (right). Tumors are indicated by arrowheads.

  • FIGURE 6.
    FIGURE 6.

    Quantitative analysis of small-animal PET/CT scans. Comparison of decay-corrected ROI analysis of 64Cu-DOTA-ZD-G1, 64Cu-DOTA-ZD-G2, and 64Cu-DOTA-ZD-G2 with coinjection of 60 μg of ZD-G2 in tumor (A), kidneys (C), and liver (D) (n = 5, **P < 0.0001). (B) Comparison of tumor-to-muscle uptake ratios after injection of 64Cu-DOTA-ZD-G1, 64Cu-DOTA-ZD-G2, and 64Cu-DOTA-ZD-G2 with coinjection of 60 μg of ZD-G2. Data shown represent mean ± SD (n = 5 per group).

  • FIGURE 7.
    FIGURE 7.

    Biodistribution at 24 h after injection of 64Cu-DOTA-ZD G1, 64Cu-DOTA-ZD-G2, and 64Cu-DOTA-ZD-G2 with coinjection of 60 μg of ZD-G2 in U-87 tumor–bearing mice. Data shown represent mean ± SD (**P < 0.0001, n = 5 per group).

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