Research ArticleTheranostics

α- Versus β-Emitting Radionuclides for Pretargeted Radioimmunotherapy of Carcinoembryonic Antigen–Expressing Human Colon Cancer Xenografts

Sandra Heskamp, Reinier Hernandez, Janneke D.M. Molkenboer-Kuenen, Markus Essler, Frank Bruchertseifer, Alfred Morgenstern, Erik J. Steenbergen, Weibo Cai, Christof Seidl, William J. McBride, David M. Goldenberg and Otto C. Boerman
Journal of Nuclear Medicine June 2017, 58 (6) 926-933; DOI: https://doi.org/10.2967/jnumed.116.187021

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Binding plot (A) and Scatchard plot (B) of 177Lu-IMP288 and 213Bi-IMP288 to TF2-pretargeted LS174T cells.

  • FIGURE 2.
    FIGURE 2.

    Biodistribution of radiolabeled IMP288. (A) 213Bi-IMP288 biodistribution in TF2- or TF12-pretargeted LS174T tumor–bearing mice at 60 min after injection. (B) Biodistribution of 213Bi-IMP288 (0.28 nmol) in mice bearing TF2-pretargeted LS174T xenografts at 15, 30, 45, and 60 min after injection. (C) Biodistribution of 213Bi-IMP288 (0.28 nmol) or 177Lu-IMP288 (0.28 nmol) in mice bearing TF2-pretargeted LS174T xenografts at 60 min after injection. p.i. = after injection.

  • FIGURE 3.
    FIGURE 3.

    Autoradiography and hematoxylin–eosin (HE) staining of LS174T tumor xenografts of mice injected with TF2 and 177Lu-IMP288. Autoradiography reveals heterogeneous uptake of 177Lu-IMP288. Areas with low uptake were found in both necrotic (A) and viable (B) tumor tissue (arrow).

  • FIGURE 4.
    FIGURE 4.

    Body weight of non–tumor-bearing mice treated with TF2 and different activity doses of 213Bi-IMP288 or 177Lu-IMP288.

  • FIGURE 5.
    FIGURE 5.

    Representative kidney slices stained with periodic acid–Schiff from mice treated with 213Bi-IMP288 or 177Lu-IMP288. Arrows indicate tubular damage in mice treated with 12 or 17 MBq 213Bi-IMP288.

  • FIGURE 6.
    FIGURE 6.

    Tumor size of mice treated with TF2 and different activity doses of 213Bi-IMP288 or 177Lu-IMP288.

  • FIGURE 7.
    FIGURE 7.

    Survival curves of mice treated with TF2 and different activity doses of 213Bi-IMP288 or 177Lu-IMP288.

Tables

  • TABLE 1

    Criteria for Assessment of Renal Damage

    GradeCriteria
    0No irregularities
    1Little dilatation of tubules; no basal membrane thickening
    2Criteria as for grade 1, but more pronounced tubule dilatation, basal membrane thickening, and mitotic activity
    3Shrinkage of small number of glomeruli; flat or lost tubule epithelium, strong tubule dilatation, and more pronounced basal membrane thickening
    4Increased shrinkage of glomeruli leading to optical emptiness; strongly dilated tubules and signs of peripheral fibrosis
  • TABLE 2

    Comparison of In Vitro Characteristics of 213Bi-IMP288 and 177Lu-IMP288

    Characteristic213Bi-IMP288177Lu-IMP288
    Cell-associated activity internalized at 3 h (mean ± SD)17.5% ± 5.3%12.1% ± 0.8%
    Dissociation constant (95% confidence interval)0.45 ± 0.20 nM0.53 ± 0.12 nM
    Maximum binding (95% confidence interval)22,182 ± 1,338 molecules per cell20,114 ± 2,164 molecules per cell

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