Bismuth-212-labeled anti-Tac monoclonal antibody: alpha-particle-emitting radionuclides as modalities for radioimmunotherapy

Journal Article · Wed Jan 01 04:00:00 EST 1986 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.83.2.474· OSTI ID:5802195

Kozak, R W; Atcher, R W; Gansow, O A; Friedman, A M; Hines, J J; Waldmann, T A

Anti-Tac, a monoclonal antibody directed to the human interleukin 2 (IL-2) receptor, has been successfully conjugated to the alpha-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 microCi/microgram (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 microCi or the equivalent of 12 rad/ml of alpha radiation targeted by anti-Tac eliminated greater than 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 alpha 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 alpha-particle-emitting radionuclides in immunotherapy.

• Research Organization: National Cancer Institute, Bethesda, MD
• OSTI ID: 5802195
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 2; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550604 -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-)
560161* -- Radionuclide Effects
Kinetics
& Toxicology-- Man
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALPHA DECAY RADIOISOTOPES
ALPHA PARTICLES
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BISMUTH 212
BISMUTH ISOTOPES
CHARGED PARTICLES
DISEASES
HEAVY NUCLEI
HEMIC DISEASES
HOURS LIVING RADIOISOTOPES
IMMUNOTHERAPY
ISOTOPES
LABELLED COMPOUNDS
LEUKEMIA
MEDICINE
MEMBRANE PROTEINS
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEAR MEDICINE
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PATIENTS
PROTEINS
RADIOISOTOPES
RADIOLOGY
RADIOTHERAPY
RECEPTORS
SPECIFICITY
THERAPY
USES