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Anti-Tac, a monoclonal antibody directed to the human interleukin 2 (IL-2) receptor, has been successfully conjugated to the a-particle-emitting radionuclide bismuth-212 by use of a bifunctional ligand, the isobutylcarboxycwrbonic 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 140 ,uCi/,ug (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 ImCi or the equivalent of 12 rad/mI of a 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 a 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 a-particle-emitting radionuclides in immunotherapy.

SummaryThe alpha half lives and energies ofGd 97.5 ± 6.5 yrs. 3.17 ± .02 MeVGd 1.78 ± (.08) • 10Sm 1.026 ± (.048) • 10The half life of