/sup 67/Ga-labeled antibodies for immunoscintigraphy and evaluation of tumor targeting of drug-antibody conjugates in mice
To assess the in vivo behavior of cytotoxic agents linked to antibodies, deferoxamine, known to form stable chelates with /sup 67/Ga, was conjugated with monoclonal antibodies using three different methods. One method used a homocoupling reagent, glutaraldehyde, whereas two other methods used heterocoupling reagents, N-succinimidyl-3-(2-pyridyldithio)propionate and succinimidyl-6-maleimidohexanoate, linking deferoxamine to antibodies through alkylamine, disulfide, and thioether bonds, respectively. Antibodies were efficiently labeled with /sup 67/Ga through chelation with deferoxamine without losing antigen-binding capability. /sup 67/Ga-labeled antibodies clearly visualized transplanted tumors in nude mice. However, the biodistribution of radioactivity was markedly different with the coupling methods used for the conjugation of deferoxamine and antibodies. High nonspecific uptake in the liver and spleen was observed with /sup 67/Ga-labeled antibodies prepared by the glutaraldehyde method. /sup 67/Ga-labeled antibodies linked by thioether bonds demonstrated in vivo stability and the highest tumor:liver ratio, whereas /sup 67/Ga-labeled antibodies conjugated with disulfide bonds were rapidly cleared from the circulation. These results indicate that antibody conjugates linked by thioether bonds are a better choice for drug targeting and that /sup 67/Ga-labeled antitumor monoclonal antibodies are useful not only for the immunoscintigraphy but also for the quantitative assessment and visualization of the biodistribution of drug-antibody conjugates.
- Research Organization:
- Kyoto Univ. (Japan)
- OSTI ID:
- 5207209
- Journal Information:
- Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 48:5; ISSN CNREA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Preparation of Ga-67 labeled monoclonal antibodies using deferoxamine as a bifunctional chelating agent
Zirconium-labeled monoclonal antibodies and their distribution in tumor-bearing nude mice
Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
CHELATING AGENTS
COUNTING TECHNIQUES
DAYS LIVING RADIOISOTOPES
DEFEROXAMINE
DIAGNOSIS
DIAGNOSTIC TECHNIQUES
DISEASES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
EXPERIMENTAL NEOPLASMS
GALLIUM 67
GALLIUM ISOTOPES
INTERMEDIATE MASS NUCLEI
ISOTOPES
LABELLING
MAMMALS
MICE
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
RADIOISOTOPE SCANNING
RADIOISOTOPES
REAGENTS
RODENTS
SCINTISCANNING
TISSUE DISTRIBUTION
UPTAKE
VERTEBRATES