Ablation of human colon carcinoma in nude mice by sup 131 I-labeled monoclonal anti-carcinoembryonic antigen antibody F(ab')2 fragments

Journal Article · Mon May 01 00:00:00 EDT 1989 · Journal of Clinical Investigation; (USA)

DOI:https://doi.org/10.1172/JCI114037· OSTI ID:5561582

Buchegger, F; Pfister, C; Fournier, K; Prevel, F; Schreyer, M; Carrel, S; Mach, J P ^[1]

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1. Ludwig Institute for Cancer Research (Switzerland)

Pooled F(ab')2 fragments of three MAbs against distinct epitopes of carcinoembryonic antigen (CEA) were used for radioimmunotherapy of nude mice bearing a subcutaneous human colon carcinoma xenograft. 9-10 d after transplantation when tumor nodules were in exponential growth, 36 mice were treated by intravenous injection of different amounts of {sup 131}I-labeled MAb F(ab')2. All 14 mice injected with a single dose of 2,200 (n = 10) or 2,800 microCi (n = 4) showed complete tumor remission. 8 of the 10 mice treated with 2,200 microCi survived in good health for 1 yr when they were killed and shown to be tumor free. Four of nine other mice treated with four fractionated doses of 400 microCi showed no tumor relapse for more than 9 mo. In contrast, all 15 mice injected with 1,600-3,000 microCi {sup 131}I-control IgG F(ab')2 showed tumor growth retardation of only 1-4 wk, and 15 of 16 mice injected with unlabeled anti-CEA MAb F(ab')2 showed unmodified tumor progression as compared with untreated mice. From tissue radioactivity distributions it was calculated that by an injection of 2,200 microCi {sup 131}I-MAb F(ab')2 a mean dose of 8,335 rad was selectively delivered to the tumor, while the tissue-absorbed radiation doses for the normal organs were: peripheral blood, 2,093; stomach, 1,668; kidney, 1,289; lung, 1,185; liver, 617; spleen, 501; small intestine, 427; large intestine, 367; bone, 337; and muscle, 198. These treatments were well tolerated since out of 19 mice with complete tumor remission only 4 required bone marrow transplantation and 17 were in good health for 6-12 mo of observation.

• OSTI ID: 5561582
• Journal Information: Journal of Clinical Investigation; (USA), Journal Name: Journal of Clinical Investigation; (USA) Vol. 83:5; ISSN 0021-9738; ISSN JCINA
• Country of Publication: United States
• Language: English

Related Subjects

550604* -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
ANTIBODIES
ANTIGENS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARCINOEMBRYONIC ANTIGEN
CARCINOMAS
CONTROL
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DOSES
EXPERIMENTAL NEOPLASMS
GASTROINTESTINAL TRACT
GLOBULINS
IMMUNOGLOBULINS
IMMUNOLOGY
IMMUNOTHERAPY
INTERMEDIATE MASS NUCLEI
INTESTINES
IODINE 131
IODINE ISOTOPES
ISOTOPES
LARGE INTESTINE
MAMMALS
MEDICINE
MICE
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PROTEINS
QUALITY CONTROL
RADIATION DOSES
RADIOIMMUNOLOGY
RADIOIMMUNOTHERAPY
RADIOISOTOPES
RADIOLOGY
RADIOTHERAPY
RODENTS
SURVIVAL CURVES
THERAPY
VERTEBRATES