Synthesis of 1-(p-isothiocyanatobenzyl) derivatives of DTPA and EDTA. Antibody labeling and tumor-imaging studies
To investigate the /sup 111/In labeling of tumor-localizing monoclonal antibodies (MoAb), the chelate 1-(p-isothiocyanatobenzyl)diethylenetriaminepentaacetic acid (p-SCN-Bz-DPTA) (1) and its EDTA analogue (2) have been synthesized. By the use of a MoAb (B72.3) specific for a high molecular weight antigen (TAG-72) on cells of a colorectal carcinoma grown in nude mice, optimal chemical conditions for MoAb conjugation of those ligands and of the dicyclic and isobutylcarboxy carbonic anhydrides of DTPA and subsequent /sup 111/In labeling were determined. All conjugates were shown by a competitive binding assay to retain their specificity and activity in vitro when less than one ligand is protein coupled both prior to and after /sup 111/In labeling. Chemical methods for purification of the MoAb were systematically investigated by injection of purified immunoprotein into athymic mice bearing LS-174T tumors that express the TAG-72 antigen. Tissue distribution studies revealed that simple addition of EDTA to labeled immunoglobulins was ineffective at complexing indium not linked to protein by chelates. Similarly, gel chromatography (Sephadex G-50) was not sufficient; rather, size exclusion HPLC had to be employed to remove unreacted /sup 111/In and aggregated antibody. To compare the relative utility of the four chelates for /sup 111/In diagnostic radioimmunoimaging, scintigraphic images of tumor-bearing mice were obtained and evaluated along with tissue distributions. Results showed that clear images of these solid tissue tumors free of extraneous radiation could be obtained only by using p-SCN-Bz-DTPA purified by HPLC. Methods developed are now being employed in clinical trials for diagnosis of human colorectal cancer. 71 references, 5 figures, 1 table.
- Research Organization:
- National Cancer Institute, Bethesda, MD
- OSTI ID:
- 7118600
- Journal Information:
- Inorg. Chem.; (United States), Journal Name: Inorg. Chem.; (United States) Vol. 25:16; ISSN INOCA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BODY
CARBOXYLIC ACIDS
CARCINOMAS
CHELATING AGENTS
CHEMICAL REACTIONS
DATA
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
DRUGS
DTPA
EDTA
ELECTRON CAPTURE RADIOISOTOPES
EXPERIMENTAL DATA
GASTROINTESTINAL TRACT
IMAGES
INDIUM 111
INDIUM ISOTOPES
INFORMATION
INTERMEDIATE MASS NUCLEI
INTESTINES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
LABELLING
LARGE INTESTINE
MAMMALS
MICE
MINUTES LIVING RADIOISOTOPES
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEI
NUMERICAL DATA
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RODENTS
VERTEBRATES