Radioimmunotherapy of peritoneal human colon cancer xenografts with site-specifically modified sup 212 Bi-labeled antibody

Journal Article · Thu Feb 01 00:00:00 EST 1990 · Cancer Research; (USA)

OSTI ID:6938076

Simonson, R B; Ultee, M E; Hauler, J A; Alvarez, V L ^[1]

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1. CYTOGEN Corporation, Princeton, NJ (USA)

212Bi is a radioisotope that emits highly cytotoxic alpha-particles. alpha-particles have a high linear energy transfer over a short path length. These properties and the 1-h half-life make this isotope suitable for radioimmunotherapy of peritoneal tumors. Therefore, we wanted to test whether monoclonal antibodies labeled with {sup 212}Bi would be effective in treating such tumors. We conjugated the antibody B72.3, which is reactive with many human adenocarcinomas, to the chelator linker glycyltyrosyl-lysyl-N-epsilon-diethylenetriaminepentaacetic acid, by reductive amination to the carbohydrate residues of the antibody. Athymic nude mice were injected i.p. with LS174T cells, a human colon cancer cell line. Seven to 13 days later the mice were treated with the {sup 212}Bi-labeled antibody. We treated the mice using single doses of 180-450 microCi or multiple doses of 80-180 microCi on consecutive days. Dissections were performed 9-16 days after the end of treatment. Both the single and multiple doses resulted in a decrease in tumor burden when compared to tumor from mice receiving unlabeled antibody. Mice in the optimum group showed tumor reductions of greater than 90%. Treatment with a {sup 212}Bi-labeled irrelevant antibody was significantly less effective than that with labeled B72.3 antibody. Survival studies showed that mice receiving the labeled antibody had a prolonged survival when compared to control mice.

• OSTI ID: 6938076
• Journal Information: Cancer Research; (USA), Vol. 50; ISSN 0008-5472
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
MONOCLONAL ANTIBODIES
SPECIFICITY
NEOPLASMS
RADIOIMMUNOTHERAPY
PERITONEUM
BIOLOGICAL HALF-LIFE
BISMUTH 212
DTPA
EXPERIMENTAL NEOPLASMS
LABELLING
LET
MICE
RADIATION DOSES
SURVIVAL CURVES
ALPHA DECAY RADIOISOTOPES
AMINO ACIDS
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BISMUTH ISOTOPES
CARBOXYLIC ACIDS
CHELATING AGENTS
DISEASES
DOSES
DRUGS
ENERGY TRANSFER
HEAVY NUCLEI
HOURS LIVING RADIOISOTOPES
IMMUNOLOGY
IMMUNOTHERAPY
ISOTOPES
MAMMALS
MEDICINE
MEMBRANES
NUCLEAR MEDICINE
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
RADIOIMMUNOLOGY
RADIOISOTOPES
RADIOLOGY
RADIOPROTECTIVE SUBSTANCES
RADIOTHERAPY
RODENTS
SEROUS MEMBRANES
THERAPY
VERTEBRATES
550604* - Medicine- Unsealed Radionuclides in Therapy- (1980-)