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Therapeutic efficacy of alpha-radioimmunotherapy with different activity levels of the Bi-213-labeled monoclonal antibody MX35 in an ovarian cancer model

Journal article
Authors Anna Gustafsson-Lutz
Tom Bäck
Emma Aneheim
Ragnar Hultborn
Stig Palm
Lars Jacobsson
A. Morgenstern
F. Bruchertseifer
Per Albertsson
Sture Lindegren
Published in EJNMMI Research
Volume 7
ISSN 2191-219X
Publication year 2017
Published at Institute of Clinical Sciences, Department of Radiation Physics
Institute of Clinical Sciences, Department of Oncology
Language en
Links dx.doi.org/10.1186/s13550-017-0283-...
Keywords Radioimmunotherapy, Dosimetry, High LET radiation, Monoclonal antibodies (mAb), CARCINOMA ASCITES-CELLS, NUDE-MICE, AT-211-MX35 F(AB')(2), LONG-TERM, PHARMACOKINETICS, MYELOTOXICITY, IRRADIATION, DOSIMETRY, BINDING, TH-229
Subject categories Cancer and Oncology

Abstract

Background: The aim of this study was to compare the therapeutic efficacy of two different activity levels of the Bi-213-labeled monoclonal antibody MX35 in an ovarian cancer model. Sixty female BALB/c (nu/nu) mice were inoculated intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40 mice were injected intraperitoneal (i.p.) with 1 ml of Bi-213-MX35, 3 MBq/mL (n = 20), or 9 MBq/mL (n = 20). An additional 20 mice received unlabeled MX35. Incidence of tumors and ascites was investigated 8 weeks after therapy. Body weight and white blood cell counts were monitored after treatment for possible signs of toxicity. Results: The tumor-free fraction of the animals treated with 3 MBq/mL of Bi-213-MX35 was 0.55, whereas that of animals treated with 9 MBq/mL of Bi-213-MX35 was 0.78. The control group treated with unlabeled MX35 had a tumor-free fraction of 0.15. No significant reduction in white blood cell counts or weight loss was observed. Conclusions: Tumor growth after i.p. treatment with Bi-213-MX35 was significantly reduced compared to treatment with unlabeled MX35. Treatment with 9 MBq/mL of Bi-213-MX35 resulted in higher tumor-free fraction compared with 3 MBq/mL of Bi-213-MX35, but this difference was not statistically significant. No signs of toxicity were observed in the treated animals.

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