title: 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.
abstract: The monoclonal humanized anti-HER2 antibody trastuzumab was radiolabeled with the positron emitter (76)Br (T(1/2) =16.2 h). Indirect labeling was performed using the p-isothiocyanatobenzene derivative of the [(76)Br]undecahydro-bromo-7,8-dicarba-nido-undecaborate(1-) ((76)Br-NBI) as a precursor molecule. (76)Br-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 microg 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.
authors.affiliation: Institute of Chemistry, Department of Organic Chemistry, Uppsala University, Sweden.
authors.forename: Karl Johan
authors.initials: KJ
authors.lastname: Winberg
authors.forename: Mikael
authors.initials: M
authors.lastname: Persson
authors.forename: Per-Uno
authors.initials: PU
authors.lastname: Malmström
authors.forename: Stefan
authors.initials: S
authors.lastname: Sjöberg
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology / Q000493:pharmacokinetics*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism*; D001967:Bromine Radioisotopes / Q000737:chemistry* / Q000276:immunology / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D004355:Drug Stability; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D016719:Radioimmunodetection / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D001967:Bromine Radioisotopes; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases