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

Katsumasa Fujiki; Yousuke Kanayama; Shinya Yano; Nozomi Sato; Takuya Yokokita; Peni Ahmadi; Yasuyoshi Watanabe; Hiromitsu Haba; Katsunori Tanaka

doi:10.1039/c8sc04747b

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

Chem Sci. 2018 Dec 21;10(7):1936-1944. doi: 10.1039/c8sc04747b. eCollection 2019 Feb 21.

Authors

Katsumasa Fujiki^{1

2}, Yousuke Kanayama³, Shinya Yano⁴, Nozomi Sato⁴, Takuya Yokokita⁴, Peni Ahmadi¹, Yasuyoshi Watanabe³, Hiromitsu Haba⁴, Katsunori Tanaka^{1

2

5}

Affiliations

¹ Biofunctional Synthetic Chemistry Laboratory , RIKEN Cluster for Pioneering Research , 2-1 Hirosawa , Wako , Saitama 351-0198 , Japan . Email: kotzenori@riken.jp.
² GlycoTargeting Research Laboratory , RIKEN Baton Zone Program , 2-1 Hirosawa , Wako , Saitama 351-0198 , Japan.
³ Laboratory for Pathophysiological and Health Science , RIKEN Center for Biosystems Dynamics Research , 6-7-3 Minatojima-minamimachi, Chuo-ku , Kobe , Hyogo 650-0047 , Japan.
⁴ Nuclear Chemistry Research Team , RIKEN Nishina Center for Accelerator-Based Science , 2-1 Hirosawa , Wako , Saitama 351-0198 , Japan.
⁵ Biofunctional Chemistry Laboratory , A. Butlerov Institute of Chemistry , Kazan Federal University , 18 Kremlyovskaya Street , Kazan 420008 , Russia.

Abstract

α-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 α-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 μg^-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.