An Improved Method for Conjugating Monoclonal Antibodies with N-Hydroxysulfosuccinimidyl DOTA
| Autor: | John E. Shively, Andrew Raubitschek, Jim Y. Kao, Anne-Line Anderson, Michael R. Lewis |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Immunoconjugates
Antibodies Neoplasm medicine.drug_class Stereochemistry medicine.medical_treatment Population Biomedical Engineering Succinimides Pharmaceutical Science Bioengineering Buffers Monoclonal antibody Heterocyclic Compounds 1-Ring Mice chemistry.chemical_compound Antigen medicine Animals Humans DOTA education neoplasms Radioisotopes Pharmacology education.field_of_study biology Isoelectric focusing Chemistry Organic Chemistry Chimerin Proteins Temperature Antibodies Monoclonal Hydrogen-Ion Concentration Carcinoembryonic Antigen Radioimmunodetection Metals Radioimmunotherapy biology.protein Isoelectric Focusing Antibody Biotechnology Conjugate |
| Zdroj: | Bioconjugate Chemistry. 12:320-324 |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/bc0000886 |
| Popis: | A simple, water-soluble procedure for conjugation of monoclonal antibodies to 1,4,7,10-tetraazacyclododecane-N,N‘,N‘‘,N‘‘‘-tetraacetic acid (DOTA) has been improved by optimizing pH, buffer, and temperature conditions for the preparation of N-hydroxysulfosuccinimidyl DOTA and its conjugation to the human/murine chimeric anti-carcinoembryonic antigen antibody cT84.66. This improved method results in a 6-fold increase in conjugation efficiency, a 3−7-fold decrease in antibody cross-linking, a more homogeneous population of conjugate species, and a 5-fold decrease in the quantities of reagents needed for conjugation. The cT84.66−DOTA conjugate was labeled to high specific activity with 111In, 90Y, 88Y, 64Cu, and 67Cu, affording near-quantitative incorporation of the majority of these radiometals. This improved conjugation procedure facilitates large-scale production and radiometal labeling of cT84.66−DOTA for clinical radioimmunotherapy trials. |
| Databáze: | OpenAIRE |
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