Localization of radiolabeled antimyeloid antibodies in a human acute leukemia xenograft tumor model

Richard H C Van Der Jagt, Christopher C. Badger, Frederick R. Appelbaum, Oliver W. Press, Dana C. Matthews, Janet F. Eary, Kenneth Krohn, Irwin D. Bernstein

Research output: Contribution to journalArticle

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Abstract

Acute myeloid leukemia is an attractive disease to treat with radiolabeled antibodies because it is radiosensitive and antibody has ready access to the marrow cavity. In order to evaluate potentially useful radiolabeled antibodies against human acute myeloid leukemia, we have developed a nude mouse xenograft model using the human acute leukemia cell line, HEL. Mice with s.c. xenografts of HEL cells received infusions of radioiodinated anti-CD33 antibody. Examination of the biodistribution of the antibody showed that uptake in the s.c. tumor was maximal [16.9% injected dose (ID)/g at 1 h after infusion) following infusion of 1-10 μg of antibody and decreased following infusion of 100 μg (6.5% ID/g at 1 h) presumably as a result of saturation of antigen sites. The radiolabel was poorly retained in tumor (4.5-8.2% ID/g at 24 h after infusion). These results were consistent with in vitro studies demonstrating rapid internalization and catabolism of the anti-CD33 antibody. Uptake in tumor could be improved by using either a radiolabel that is retained intracellularly, 111In-DTPA (18.5% ID/g at 24 h), or by targeting a surface antigen that does not internalize upon antibody binding, CD45 (20.5% ID/g at 24 h). These results indicate that this model system will be useful in evaluating the interaction of radiolabeled antibodies with human acute myeloid leukemia cells in an in vivo setting.

Original languageEnglish (US)
Pages (from-to)89-94
Number of pages6
JournalCancer Research
Volume52
Issue number1
StatePublished - Jan 1 1992
Externally publishedYes

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Heterografts
Leukemia
Antibodies
Neoplasms
Acute Myeloid Leukemia
Anti-Idiotypic Antibodies
Pentetic Acid
Myeloid Cells
Surface Antigens
Nude Mice
Bone Marrow
Antigens
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Van Der Jagt, R. H. C., Badger, C. C., Appelbaum, F. R., Press, O. W., Matthews, D. C., Eary, J. F., ... Bernstein, I. D. (1992). Localization of radiolabeled antimyeloid antibodies in a human acute leukemia xenograft tumor model. Cancer Research, 52(1), 89-94.

Localization of radiolabeled antimyeloid antibodies in a human acute leukemia xenograft tumor model. / Van Der Jagt, Richard H C; Badger, Christopher C.; Appelbaum, Frederick R.; Press, Oliver W.; Matthews, Dana C.; Eary, Janet F.; Krohn, Kenneth; Bernstein, Irwin D.

In: Cancer Research, Vol. 52, No. 1, 01.01.1992, p. 89-94.

Research output: Contribution to journalArticle

Van Der Jagt, RHC, Badger, CC, Appelbaum, FR, Press, OW, Matthews, DC, Eary, JF, Krohn, K & Bernstein, ID 1992, 'Localization of radiolabeled antimyeloid antibodies in a human acute leukemia xenograft tumor model', Cancer Research, vol. 52, no. 1, pp. 89-94.
Van Der Jagt RHC, Badger CC, Appelbaum FR, Press OW, Matthews DC, Eary JF et al. Localization of radiolabeled antimyeloid antibodies in a human acute leukemia xenograft tumor model. Cancer Research. 1992 Jan 1;52(1):89-94.
Van Der Jagt, Richard H C ; Badger, Christopher C. ; Appelbaum, Frederick R. ; Press, Oliver W. ; Matthews, Dana C. ; Eary, Janet F. ; Krohn, Kenneth ; Bernstein, Irwin D. / Localization of radiolabeled antimyeloid antibodies in a human acute leukemia xenograft tumor model. In: Cancer Research. 1992 ; Vol. 52, No. 1. pp. 89-94.
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