Radiotherapy of CD19 Expressing Daudi Tumors in Nude Mice with Yttrium-90-Labeled Anti-CD19 Antibody

Daniel A. Vallera, Michael Elson, Martin W. Brechbiel, Kathryn E. Dusenbery, Linda J. Burns, Waclaw B. Jaszcz, Norma K. Ramsay, Angela Panoskaltsis-Mortar, David W. Kuroki, John E. Wagner, Ellen S. Vitetta, John H. Kersey

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Studies were performed to determine the suitability of using two different anti-CD19 monoclonal antibodies to deliver the high energy beta-particle emitting isotope 90Y to B-cell lymphoma grown as flank tumors in athymic nude mice. The antibodies BU12 and HD37, both of the IgG1 subclass, recognize CD19, an internalizing B-lineage-specific membrane glycoprotein and member of the Ig supergene family. The antibodies were readily labeled with 90Y using the highly stable chelate, 1B4M-MX-DTPA. The radioimmunoconjugates selectively bound to the CD19 expressing B cell line Daudi, but not to CD19 negative control cells. Significantly more 90Y anti-CD19 bound to Daudi tumors growing in nude mice than did a control non-binding antibody (p = 0.001). The biodistribution data correlated with an anti-tumor effect. Anti-tumor activity was dose dependent and the best results were observed in mice receiving a single dose of approximately 300 uCi. The anti-CD19 antibody had significantly better anti-tumor activity as compared to a control 90Y-labeled antibody and most mice survived over 119 days with no evidence of tumor (p < 0.003). Histology studies showed no significant injury to the kidney, liver, or small intestine. Because radiolabeled anti-CD19 antibody can be used to deliver radiation selectively to lymphohematopoietic tissue, these data support the use of 90Y anti-CD19 antibodies in treating B-cell malignancies.

Original languageEnglish (US)
Pages (from-to)11-23
Number of pages13
JournalCancer Biotherapy and Radiopharmaceuticals
Volume19
Issue number1
DOIs
StatePublished - 2004

Keywords

  • Anti-CD19
  • Bone marrow transplantation
  • Leukemia
  • Nude mice
  • Radioimmunoconjugate
  • Radiopharmaceutical
  • Tumor
  • Y

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research

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  • Cite this

    Vallera, D. A., Elson, M., Brechbiel, M. W., Dusenbery, K. E., Burns, L. J., Jaszcz, W. B., Ramsay, N. K., Panoskaltsis-Mortar, A., Kuroki, D. W., Wagner, J. E., Vitetta, E. S., & Kersey, J. H. (2004). Radiotherapy of CD19 Expressing Daudi Tumors in Nude Mice with Yttrium-90-Labeled Anti-CD19 Antibody. Cancer Biotherapy and Radiopharmaceuticals, 19(1), 11-23. https://doi.org/10.1089/108497804773391630