Bismuth-212-Labeled Anti-Tac Monoclonal Antibody: α -Particle-Emitting Radionuclides as Modalities for Radioimmunotherapy

• Published in: Proceedings of the National Academy of Sciences - PNAS 1986-01, Vol.83 (2), p.474-478
• Main Authors: Kozak, Robert W., Atcher, Robert W., Gansow, Otto A., Friedman, Arnold M., Hines, John J., Waldmann, Thomas A.
• Format: Article
• Language: English
• Subjects: Antibodies; Antibodies, Monoclonal - therapeutic use; B lymphocytes; Biological and medical sciences; Bismuth - therapeutic use; Cell Line; Cell lines; Combined treatment; Cytotoxicity; Cytotoxicity, Immunologic; Humans; Immunotherapy; Leukemia - therapy; Medical sciences; Monoclonal antibodies; Protein synthesis; Radiation dosage; Radioisotopes; Radionuclides; Receptors; Receptors, Immunologic - immunology; Receptors, Interleukin-2; T lymphocytes; T-Lymphocytes - immunology; Treatment. General aspects; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.83.2.474

Anti-Tac, a monoclonal antibody directed to the human interleukin 2 (IL-2) receptor, has been successfully conjugated to the α -particle-emitting radionuclide bismuth-212 by use of a bifunctional ligand, the isobutylcarboxycarbonic anhydride of diethylenetriaminepentaacetic acid. The physical properties of 212Bi are appropriate for radioimmunotherapy in that it has a short half-life, deposits its high energy over a short distance, and can be obtained in large quantities from a radium generator. Antibody specific activities of 1-40 μ Ci/μ g (1 Ci = 37 GBq) were achieved. Specificity of the 212Bi-labeled anti-Tac was demonstrated for the IL-2 receptor-positive adult T-cell leukemia line HUT-102B2 by protein synthesis inhibition and clonogenic assays. Activity levels of 0.5 μ Ci or the equivalent of 12 rad/ml of α radiation targeted by anti-Tac eliminated >98% the proliferative capabilities of HUT-102B2 cells with more modest effects on IL-2 receptor-negative cell lines. Specific cytotoxicity was blocked by excess unlabeled anti-Tac but not by human IgG. In addition, an irrelevant control monoclonal antibody of the same isotype labeled with 212Bi was unable to target α radiation to cell lines. Therefore, 212Bi-labeled anti-Tac is a potentially effective and specific immunocytotoxic reagent for the elimination of IL-2 receptor-positive cells. These experiments thus provide the scientific basis for use of α -particle-emitting radionuclides in immunotherapy.