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Localization of Radiolabeled Antimyeloid Antibodies in a Human Acute Leukemia Xenograft Tumor Model¹

Programs in Pediatric [R. H. C. v. d. J., D. C. M., I. D. B.] and Medical [C. C. B., F. R. A., O. W. P.] Oncology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, and Departments of Medicine [C. C. B., F. R. A., O. W. P.], Pediatrics [D. C. M., I. D. B.], and Radiology [J. F. E., K. A. K.], University of Washington, Seattle, Washington 98195

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.

¹ Supported by NIH Grants CA26386 and CA18105 and DOE Grant DE-F-G06,88ER60711.

² Recipient of a McEarhern Fellowship from the Canadian Cancer Society. Present address: Department of Hematology, Ottawa General Hospital, University of Ottawa, Ottawa, Ontario KIH 8L6, Canada.

³ To whom requests for reprints should be addressed, at Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, WA 98104.

Received 6/24/91. Accepted 10/22/91.

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