title: Radiobromination of monoclonal antibody using potassium [76Br] (4 isothiocyanatobenzyl-ammonio)-bromo-decahydro-closo-dodecaborate (Bromo-DABI).
abstract: The use of charged linkers in attaching radiohalogens to tumor-seeking biomolecules may improve intracellular retention of the radioactive label after internalization and degradation of targeting proteins. Derivatives of polyhedral boron clusters, such as closo-dodecaborate (2-) anion, might be possible charged linkers. In this study, a bifunctional derivative of closo-dodecaborate, (4-isothiocyanatobenzyl-ammonio)-undecahydro-closo-dodecaborate (DABI) was labeled with positron-emitting nuclide (76)Br (T 1/2 = 16.2 h) and coupled to anti-HER2/neu humanized antibody Trastuzumab. The overall labeling yield at optimized conditions was 80.7 +/- 0.6%. The label was proven to be stable in vitro in physiological and a set of denaturing conditions. The labeled antibody retained its capacity to bind to HER-2/neu antigen expressing cells. The results of the study demonstrated feasibility for using derivatives of closo-dodecaborate in indirect labeling of antibodies for radioimmunoPET.
authors.affiliation: Unit of Biomedical Radiation Sciences, Rudbecklaboratoriet, Uppsala University, S-751 85, Uppsala, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bruskin
authors.forename: Igor
authors.initials: I
authors.lastname: Sivaev
authors.forename: Mikael
authors.initials: M
authors.lastname: Persson
authors.forename: Hans
authors.initials: H
authors.lastname: Lundqvist
authors.forename: Jörgen
authors.initials: J
authors.lastname: Carlsson
authors.forename: Stefan
authors.initials: S
authors.lastname: Sjöberg
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000493:pharmacokinetics*; D001896:Boron Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D004355:Drug Stability; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D008657:Metabolic Clearance Rate; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics
chemical_list: D000911:Antibodies, Monoclonal; D001896:Boron Compounds; D019275:Radiopharmaceuticals; C493095:bromo-(4-isothiocyanatobenzyl-ammonio)-undecahydro-closo-dodecaborate