Aminooxy‐functionalized DOTA for radiolabeling of oxidized antibodies: evaluation of site‐specific 111In‐labeled trastuzumab

摘要: Antibody-targeted nuclear imaging or radiotherapy rely on chemical modification of the polypeptide backbone that may hamper antigen binding and hence targeting ability. In this study, we examine a strategy for covalent radiolabeling monoclonal antibodies utilizing oligosaccharide moieties molecule: 111In-radiolabeling antibody trastuzumab (Herceptin®, Roche, Basel, Switzerland), which targets breast cancer-related ErbB2/human epidermal growth factor-2 (HER2) protein. The site-specific radiolabeled was obtained through mild oxidation Fc region with periodate its conjugation an aminooxy-functionalized tetraazacyclododecanetetraacetic acid (DOTA) chelator. It further evaluated both in vitro HER2 expressing cells vivo tumor-bearing mice by single photon emission computed tomography (SPECT), compared DOTA-N-hydroxysuccinimide methodology. Such did not show significant difference stability when lysine-conjugated (>95%, 3 days postinjection). They also maintain their immunoreactivity (>90% immunoreactive fraction) affinity (Kd ~ 4–5 nM) (12.9 %ID/g MDA-MB-361 tumors). Our results confirm formation hydrolytically stable oxime linker between chelating agent oxidized N-glycan residues, away from variable antigen-binding sites, is attractive approach accessing radiopharmaceuticals immunotherapeutics. Copyright © 2012 John Wiley & Sons, Ltd.