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Research ArticleBasic Science Investigations

213Bi Radioimmunotherapy with an Anti-mCD138 Monoclonal Antibody in a Murine Model of Multiple Myeloma

Michel Chérel, Sébastien Gouard, Joëlle Gaschet, Catherine Saï-Maurel, Frank Bruchertseifer, Alfred Morgenstern, Mickael Bourgeois, Jean-François Gestin, Françoise Kraeber Bodéré, Jacques Barbet, Philippe Moreau and François Davodeau
Journal of Nuclear Medicine September 2013, 54 (9) 1597-1604; DOI: https://doi.org/10.2967/jnumed.112.111997
Michel Chérel
1Nantes-Angers Cancer Research Center CRCNA, University of Nantes, INSERM UMR892, CNRS UMR6299, Nantes, France
2Nuclear Medicine Department, ICO-René Gauducheau Cancer Center, IRCNA, Saint Herblain, France
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Sébastien Gouard
1Nantes-Angers Cancer Research Center CRCNA, University of Nantes, INSERM UMR892, CNRS UMR6299, Nantes, France
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Joëlle Gaschet
1Nantes-Angers Cancer Research Center CRCNA, University of Nantes, INSERM UMR892, CNRS UMR6299, Nantes, France
2Nuclear Medicine Department, ICO-René Gauducheau Cancer Center, IRCNA, Saint Herblain, France
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Catherine Saï-Maurel
1Nantes-Angers Cancer Research Center CRCNA, University of Nantes, INSERM UMR892, CNRS UMR6299, Nantes, France
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Frank Bruchertseifer
3European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe, Germany
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Alfred Morgenstern
3European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe, Germany
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Mickael Bourgeois
1Nantes-Angers Cancer Research Center CRCNA, University of Nantes, INSERM UMR892, CNRS UMR6299, Nantes, France
4Nuclear Medicine Department, University Hospital, Nantes, France; and
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Jean-François Gestin
1Nantes-Angers Cancer Research Center CRCNA, University of Nantes, INSERM UMR892, CNRS UMR6299, Nantes, France
2Nuclear Medicine Department, ICO-René Gauducheau Cancer Center, IRCNA, Saint Herblain, France
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Françoise Kraeber Bodéré
1Nantes-Angers Cancer Research Center CRCNA, University of Nantes, INSERM UMR892, CNRS UMR6299, Nantes, France
2Nuclear Medicine Department, ICO-René Gauducheau Cancer Center, IRCNA, Saint Herblain, France
4Nuclear Medicine Department, University Hospital, Nantes, France; and
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Jacques Barbet
1Nantes-Angers Cancer Research Center CRCNA, University of Nantes, INSERM UMR892, CNRS UMR6299, Nantes, France
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Philippe Moreau
1Nantes-Angers Cancer Research Center CRCNA, University of Nantes, INSERM UMR892, CNRS UMR6299, Nantes, France
5Hematology Department, University Hospital, Nantes, France
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François Davodeau
1Nantes-Angers Cancer Research Center CRCNA, University of Nantes, INSERM UMR892, CNRS UMR6299, Nantes, France
4Nuclear Medicine Department, University Hospital, Nantes, France; and
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  • FIGURE 1.
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    FIGURE 1.

    Bioluminescence imaging of early invasion of 5T33-Luc+ MM cells in C57BL/KaLwRij mice. Images were obtained by bioluminescence at 12 (A), 20 (B), and 44 (C) days after intravenous injection of 106 5T33-Luc+ cells. Imaging was performed under general anesthesia and 5 min after intraperitoneal injection of luciferin.

  • FIGURE 2.
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    FIGURE 2.

    Biodistribution of 111In-anti-mCD138 in C57BL/KaLwRij mice. Biodistribution of 111In-anti-mCD138 in %ID/g in different tissues 90 min after injection of 111In-anti-mCD138.

  • FIGURE 3.
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    FIGURE 3.

    Kaplan–Meier survival curves of C57BL/KaLwRij mice grafted with 106 5T33 MM cells treated with 213Bi-anti-mCD138 at 1.85, 3.7, 7.4, and 11.1 MBq and irrelevant mAb at 3.7 MBq and PBS.

  • FIGURE 4.
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    FIGURE 4.

    Immunomonitoring of blood mAb produced by 5T33 MM cells in response to 213Bi-anti-mCD138 at 1.85, 3.7, and 7.4 MBq and PBS control. Isotype-specific ELISA was used to monitor plasma monoclonal Ig levels over 22 wk. RIT = radioimmunotherapy.

  • FIGURE 5.
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    FIGURE 5.

    Monitoring weight and liver (with ASAT and ALAT) and kidney (with creatinine) toxicities in plasma of C57BL/KaLwRij mice grafted with 106 5T33 MM cells treated with 213Bi-anti-mCD138 at 3.7 and 7.4 MBq and PBS. Mice were weighed weekly over 20 wk after radioimmunotherapy. Results are expressed as percentage of initial weight at day 0 (A). At each time point, creatinine (B), ASAT (C), and ALAT (D) were measured in pool of equal volume of plasma of surviving mice for mice injected with 3.7 MBq, 7.4 MBq, and PBS (0 MBq). RIT = radioimmunotherapy.

  • FIGURE 6.
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    FIGURE 6.

    Hematologic toxicity analysis of C57BL/KaLwRij mice grafted with 106 5T33 MM cells treated with 213Bi-anti-mCD138. Mice treated at 3.7 (○), 7.4 (△), 11.1 MBq (□), and PBS control (bar). Hematologic toxicity was evaluated in surviving mice for each experimental group after radioimmunotherapy. Leukocytes (A), platelets (B), and red blood cells (C) were analyzed weekly over 8 wk using quantitative automated hematology analyzer. (D) Plasma Flt3-L concentration after radioimmunotherapy for animals receiving 3.7 and 7.4 MBq of 213Bi-anti-mCD138 and PBS control have been measured by specific ELISA. Results are given as means and SD of 4 animals per group. RIT = radioimmunotherapy.

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Journal of Nuclear Medicine: 54 (9)
Journal of Nuclear Medicine
Vol. 54, Issue 9
September 1, 2013
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213Bi Radioimmunotherapy with an Anti-mCD138 Monoclonal Antibody in a Murine Model of Multiple Myeloma
Michel Chérel, Sébastien Gouard, Joëlle Gaschet, Catherine Saï-Maurel, Frank Bruchertseifer, Alfred Morgenstern, Mickael Bourgeois, Jean-François Gestin, Françoise Kraeber Bodéré, Jacques Barbet, Philippe Moreau, François Davodeau
Journal of Nuclear Medicine Sep 2013, 54 (9) 1597-1604; DOI: 10.2967/jnumed.112.111997

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213Bi Radioimmunotherapy with an Anti-mCD138 Monoclonal Antibody in a Murine Model of Multiple Myeloma
Michel Chérel, Sébastien Gouard, Joëlle Gaschet, Catherine Saï-Maurel, Frank Bruchertseifer, Alfred Morgenstern, Mickael Bourgeois, Jean-François Gestin, Françoise Kraeber Bodéré, Jacques Barbet, Philippe Moreau, François Davodeau
Journal of Nuclear Medicine Sep 2013, 54 (9) 1597-1604; DOI: 10.2967/jnumed.112.111997
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Keywords

  • radioimmunotherapy
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  • multiple myeloma
  • CD138
  • 5T33
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