Research ArticleTranslational
Open Access

A Tumor-Imaging Method Targeting Cancer-Associated Fibroblasts

Anastasia Loktev, Thomas Lindner, Walter Mier, Jürgen Debus, Annette Altmann, Dirk Jäger, Frederik Giesel, Clemens Kratochwil, Philippe Barthe, Christian Roumestand and Uwe Haberkorn
Journal of Nuclear Medicine September 2018, 59 (9) 1423-1429; DOI: https://doi.org/10.2967/jnumed.118.210435

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    (A) Binding of radiolabeled FAPI-01 and FAPI-02 to the 4 human cancer cell lines and to the HT-1080-FAP, HEK-muFAP, and HEK-CD26 cell lines after 60 min of incubation. (B) Internalization of radiolabeled FAPI-01 and FAPI-02 into HT-1080-FAP cells after incubation for 10 min to 24 h. Internalized fraction is gray or black, and extracellularly bound fraction is white. (C) Competitive binding of radiolabeled FAPI-01 and FAPI-02 to HT-1080-FAP cells after adding increasing concentrations of unlabeled FAPI-01 and Lu-FAPI-02. (D) Efflux kinetics of FAPI-01 and FAPI-02 after 1 h of incubation of HT-1080-FAP cells with radiolabeled compounds, followed by incubation with compound-free medium for 1–24 h. All data are %ID normalized to 1 million (mio) cells.

  • FIGURE 2.
    FIGURE 2.

    Internalization of FAPI-02 into HT-1080-FAP cells, HEK-muFAP cells, and HEK-CD26 cells after incubation for 2 h. Blue indicates 4′,6-diamidino-2-phenylindole, and green indicates FAPI-02-Atto488.

  • FIGURE 3.
    FIGURE 3.

    68Ga-FAPI-02 PET in mice bearing FAP-negative (Capan-2) (A) and human FAP-expressing (HT-1080-FAP) (B) xenografts. Images were obtained at the indicated times after injection and show rapid uptake in tumor (arrows), no accumulation in noncancerous tissue, and rapid elimination via kidneys and bladder. Quantification of PET images shows solid clearance from cardiovascular system and constant uptake into tumor.

  • FIGURE 4.
    FIGURE 4.

    (A) Blocking of 68Ga-FAPI-02 tumor accumulation by coadministration of 30 nmol of unlabeled FAPI-02 in mice bearing HT-1080-FAP tumors. (B) Time–activity curves for 68Ga-FAPI-02 in selected organs after administration with and without unlabeled FAPI-02 as competitor.

  • FIGURE 5.
    FIGURE 5.

    (A) Ex vivo biodistribution of 177Lu-FAPI-02 after administration to mice bearing HT-1080-FAP tumors. Tumor uptake is highest after 2 h (4.7 %ID/g). (B) Pharmacokinetic profile of 177Lu-FAPI-02 up to 24 h after administration.

  • FIGURE 6.
    FIGURE 6.

    PET/CT maximum-intensity projections of patient with metastasized pancreatic cancer (A) and patient with breast cancer (C). (B) Maximum uptake of 68Ga-FAPI-02 at 10 min, 1 h, and 3 h after administration to breast cancer patient. Me = metastases.

  • FIGURE 7.
    FIGURE 7.

    PET/CT maximum-intensity projections (top) and transaxial views (bottom) 1 h after administration of 18F-FDG (A) and 68Ga-FAPI-02 (B) to patient with locally advanced lung adenocarcinoma. 68Ga-FAPI-02 is seen to selectively accumulate in FAP-expressing tissue and to be significantly higher than 18F-FDG in malignant lesions. Unlike 18F-FDG, 68Ga-FAPI-02 shows no uptake in brain, spleen, or liver.

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