Research ArticleBasic Science Investigation

Pretargeted 177Lu Radioimmunotherapy of Carcinoembryonic Antigen–Expressing Human Colonic Tumors in Mice

Rafke Schoffelen, Winette T.A. van der Graaf, Gerben Franssen, Robert M. Sharkey, David M. Goldenberg, William J. McBride, Edmund A. Rossi, Annemarie Eek, Wim J.G. Oyen and Otto C. Boerman
Journal of Nuclear Medicine November 2010, 51 (11) 1780-1787; DOI: https://doi.org/10.2967/jnumed.110.079376

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    (A and B) Biodistribution and specific tumor targeting of escalating bsmAb doses (1.0–10.0 nmol of 125I-TF2, 0.4 MBq) in BALB/c nude mice with 0.02- to 0.2-g subcutaneous LS174T tumors. bsmAb was followed by injection of 0.10 nmol of IMP288 16 h later, and 1 h after that injection, mice were euthanized. (C and D) Biodistribution and specific tumor targeting of escalating peptide doses (0.035–0.41 nmol of 111In-IMP288, 0.4 MBq), injected 16 h after pretargeting with TF2 (5.0 nmol). Specific tumor targeting of 125I-TF2 and 111In-IMP288 was calculated as nmol per gram of tumor, corrected for blood concentration. Values represent mean ± SD (n = 5).

  • FIGURE 2.
    FIGURE 2.

    Accumulation and retention of 125I-TF2 (A) and 111In-IMP288 (B) in BALB/c nude mice with subcutaneous LS174T tumors. TF2 (5.0 nmol) and IMP288 (0.28 nmol) were injected, and animals underwent necropsy at 1, 6, 24, and 48 h after 111In-IMP288 injection. Values represent mean ± SD (n = 5). p.i. = after injection.

  • FIGURE 3.
    FIGURE 3.

    Biodistribution of successive 3-hourly administrations of 111In-IMP288 (A), and of successive 3-daily cycles of TF2 combined with 111In-IMP288 (B). (A) Three groups of 5 mice received 1 injection of 5.0 nmol of TF2 and 16 h later 1, 2, or 3 injections of 0.28 nmol of IMP288, with each IMP288 injection separated by 3 h. (B) Three groups of 5 mice received 1, 2, or 3 cycles of 5.0 nmol of TF2 and 0.28 nmol of IMP288, with each cycle separated by 72 h. In each group, last (or only) dose of IMP288 was labeled with 111In. One hour after IMP288 injection of labeled peptide, all mice were euthanized. Values represent mean ± SD (n = 5).

  • FIGURE 4.
    FIGURE 4.

    Tumor growth in mice that received 1, 2, or 3 cycles of TF2 (5.0 nmol) and 177Lu-IMP288 (26 MBq/0.28 nmol per cycle) or PBS. Size of tumors of individual mice is depicted.

  • FIGURE 5.
    FIGURE 5.

    Survival of animals in groups of 9 mice that were treated with 1, 2, or 3 treatment cycles of TF2 (5.0 nmol) and 177Lu-IMP288 (26 MBq/0.28 nmol per cycle) or PBS.

  • FIGURE 6.
    FIGURE 6.

    Leukocyte counts (A), platelet counts (B), and serum creatinine levels (C) in mice that were treated with 2 or 3 cycles of TF2 (5.0 nmol) and 177Lu-IMP288 (26 MBq/0.28 nmol per cycle). Blood cell counts were measured before therapy and at 2, 3, and 7 wk after injection. Serum creatinine levels were measured before therapy and at 5 and 8 wk after therapy. Data represent individual determinations.

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