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

Journal Article · Thu Feb 01 04:00:00 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), Journal Name: Cancer Research; (USA) Vol. 50; ISSN 0008-5472; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

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