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

The monoclonal humanized anti-HER2 antibody trastuzumab was radiolabeled with the positron emitter Br-76 (T-1/2 = 16.2 h). Indirect labeling was performed using the p-isothiocyanatobenzene derivative of the [Br-76]undecahydro-bromo-7,8-dicarba-nido-undecaborate(1-) (Br-76-NBI) as a precursor molecule. Br-76-NBI was prepared by bromination of the 7-(p-isothiocyanato-phenyl)dodecahydro-7,8-dicarbanido-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 mug of antibody was labeled. The label was stable in vitro in physiological and denaturing conditions. In a cell binding test, trastuzurnab remained irninunoreactive after labeling. (C) 2004 Elsevier Inc. All rights reserved.