Research ArticleOncology

Clinical Translation of a 68Ga-Labeled Integrin αvβ6–Targeting Cyclic Radiotracer for PET Imaging of Pancreatic Cancer

Xun Feng, Yanpu Wang, Dehua Lu, Xiaoxia Xu, Xin Zhou, Huiyuan Zhang, Ting Zhang, Hua Zhu, Zhi Yang, Fan Wang, Nan Li and Zhaofei Liu
Journal of Nuclear Medicine October 2020, 61 (10) 1461-1467; DOI: https://doi.org/10.2967/jnumed.119.237347

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    (A) Chemical structure of DOTA-cycratide. (B) Inhibition of 64Cu-cycratide binding to integrin αvβ6 on BxPC-3 cells by cycratide, DOTA-cycratide, and linear-pep. Data are shown as mean ± SD, n = 4. (C) Binding of 68Ga-cycratide to BxPC-3 with or without blocking of cold cycratide or linear-pep. %AD/106 cells = percentage of total added dose per million cells. Data are shown as mean ± SD, n = 4. (D) Metabolic stability of 68Ga-cycratide in blood and urine of BALB/c mice (data are representative of 3 independent experiments). **P < 0.01.

  • FIGURE 2.
    FIGURE 2.

    (A) Small-animal PET images obtained at 0.5, 1, and 2 h after injection of 68Ga-cycratide or 68Ga-linear-pep in BxPC-3 tumor–bearing mice without or with blocking doses of cold cycratide or linear-pep. Tumors are indicated by arrows. (B) Quantification of tumor uptake and tumor-to-muscle ratio of 68Ga-cycratide and 68Ga-linear-pep shown in A. Data are shown as mean ± SD, n = 4. (C) Biodistribution of 68Ga-cycratide or 68Ga-DOTA-linear-pep in BxPC-3 tumor–bearing mice without or with blocking dose of cold cycratide. Data are shown as mean ± SD, n = 4. *P < 0.05. **P < 0.01.

  • FIGURE 3.
    FIGURE 3.

    (A) PET imaging of orthotopic pancreatic cancer lesions in nude mice at 0.5 h after injection of 68Ga-cycratide without or with blocking dose of cold cycratide. Tumors are indicated by arrows. (B) Hematoxylin and eosin (H&E) staining of tumor tissues harvested from orthotopic tumor model. (C) Left, immunofluorescence staining of integrin αvβ6 from tumor tissues harvested from orthotopic tumor model. Right, negative control with secondary antibody only.

  • FIGURE 4.
    FIGURE 4.

    Multiple-time-point whole-body maximum-intensity-projection PET images of male healthy volunteer after injection of 68Ga-cycratide.

  • FIGURE 5.
    FIGURE 5.

    (A) PET/CT images of female patient with suspected pancreatic cancer. Images were obtained at 1 h after intravenous administration of 68Ga-cycratide or 18F-FDG. Tumors are indicated by arrows. (B) Immunohistochemical (IHC) staining for integrin αvβ6 in tumor sample from same patient as in A. (C) Contrast-enhanced CT (CECT) image and PET/CT images of male patient with pancreatic cancer 7 mo after surgery at 1 h after administration of 68Ga-cycratide or 18F-FDG, as well as CECT image of same patient 3 mo later (10 mo after surgery). Occupancy lesions in CT are indicated by arrows.

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