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Specific Radioimmunotherapy Using ⁹⁰Y-labeled Monoclonal Antibody in Erythroleukemic Mice¹

Departments of Pharmacology and Molecular Sciences [W. T. A., M. S.] and Comparative Medicine [R. A. S.], The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Radioimmunotherapy using ⁹⁰Y-labeled diethylenetriamine pentaacetic acid-antibody conjugates was studied in Rauscher erythroleukemia virus-infected mice. Preliminary experiments showed that biodistribution profiles for nonrelevant mouse monoclonal antibody and polyclonal bovine immunoglobulin were identical in both normal and leukemic mice. Therefore, bovine immunoglobulin G was selected as the control immunoglobulin in order to permit comparison to current clinical trials of radioimmunotherapy regimens. Specific monoclonal antibody was two-to three-fold more potent than bovine immunoglobulin G in therapy, as assessed by reduction of splenomegaly (dose required for half-maximal effect, 9 µCi versus 16 to 27 µCi). Mice treated with 50 µCi ⁹⁰Y-labeled control immunoglobulin had spleens which were twice the normal size and showed extensive areas of erythropoiesis indicative of the presence of tumor foci; in contrast, doses as low as 27 µCi ⁹⁰Y-labeled specific antibody resulted in complete remission with no microscopic evidence of tumor foci in either spleen or liver. Although reversible marrow toxicity was observed it was not dose limiting. These results demonstrate that tumor-specific therapy is possible using ⁹⁰Y-labeled antibody.

¹ This research was supported by National Cancer Institute Contract 2 R01 CA33470-04 and USPHS Grant RR00130.

² Supported by NIH Medical Scientists Training Program Grant GM07309.

³ To whom requests for reprints should be addressed.

Received 2/20/86. Revised 8/ 5/86. Revised 12/11/86. Accepted 12/29/86.