Radiobromination of anti-HER2/neu/ErbB-2 monoclonal antibody using the p-isothiocyanatobenzene derivative of the [ 76Br]undecahydro-bromo-7,8-dicarba- nido-undecaborate(1-) ion

• Published in: Nuclear medicine and biology 2004-05, Vol.31 (4), p.425-433
• Main Authors: Winberg, Karl Johan, Persson, Mikael, Malmström, Per-Uno, Sjöberg, Stefan, Tolmachev, Vladimir
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacokinetics; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - immunology; Breast Neoplasms - metabolism; Breast Neoplasms/immunology/metabolism/radionuclide imaging; Bromine Radioisotopes - chemistry; Bromine Radioisotopes - immunology; Bromine Radioisotopes - pharmacokinetics; Bromine Radioisotopes/chemistry/immunology/pharmacokinetics; Bromine-76; Cell Line, Tumor; Chemistry; Drug Stability; Humans; Isotope Labeling - methods; Kemi; Monoclonal antibodies; NATURAL SCIENCES; NATURVETENSKAP; nido-Carborate derivatives; Organic chemistry; Organisk kemi; Prosthetic group; Radiobromination; Radioimmunodetection - methods; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - chemistry; Radiopharmaceuticals - pharmacokinetics; Radiopharmaceuticals/chemical synthesis/chemistry/pharmacokinetics; Receptor, ErbB-2 - immunology; Receptor, ErbB-2 - metabolism; Trautzumab
• ISSN: 0969-8051; 1872-9614; 1872-9614
• DOI: 10.1016/j.nucmedbio.2003.11.007

The monoclonal humanized anti-HER2 antibody trastuzumab was radiolabeled with the positron emitter 76Br (T 1 2 =16.2 h). Indirect labeling was performed using the p-isothiocyanatobenzene derivative of the [ 76Br]undecahydro-bromo-7,8-dicarba- nido-undecaborate(1-) ( 76Br-NBI) as a precursor molecule. 76Br-NBI was prepared by bromination of the 7-( p-isothiocyanato-phenyl)dodecahydro-7,8-dicarba- nido-undecaborate(1−) ion (NBI) with a yield of 93-95% using Chloramine-T (CAT) as an oxidant. Coupling of radiobrominated NBI to antibody was performed without intermediate purification, in an “one pot” reaction. An overall labeling yield of 55.7 ± 4.8% (mean ± maximum error) was achieved when 300 μg of antibody was labeled. The label was stable in vitro in physiological and denaturing conditions. In a cell binding test, trastuzumab remained immunoreactive after labeling.