211At-labeled immunoconjugate via a one-pot three-component double click strategy: practical access to ?-emission cancer radiotherapeutics.

ABSTRACT: ?-Emission radiotherapeutics has potential to be one of most effective cancer therapeutics. Herein, we report a facile synthesis of an 211At-labeled immunoconjugate for use as an ?-emission molecular targeting therapy. We synthesized a tetrazine probe modified with closo-decaborate(2-), a prosthetic group that forms a bioavailable stable complex with 211At. Our one-pot three-component double-click labeling method was used to attach decaborate to trastuzumab (anti-HER2 antibody) using decaborate-tetrazine and TCO-aldehyde probes without reducing the antibody binding affinity. Labeling the decaborate-attached trastuzumab with 211At produced in the cyclotron at the RIKEN Nishina Center, at which highly radioactive 211At can be produced, readily furnished the 211At-labeled trastuzumab with a maximum specific activity of 15 MBq ?g-1 and retention of the native binding affinity. Intratumor injection of the 211At-labeled trastuzumab in BALB/c nude mice implanted with HER2-expressing epidermoid cancer cells yielded efficient accumulation at the targeted tumor site as well as effective suppression of tumor growth.

SUBMITTER: Fujiki K 

PROVIDER: S-EPMC6385556 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature