Stabilization of an 211At-Labeled Antibody with Sodium Ascorbate

Shino Manabe; Hiroki Takashima; Kazunobu Ohnuki; Yoshikatsu Koga; Ryo Tsumura; Nozomi Iwata; Yang Wang; Takuya Yokokita; Yukiko Komori; Sachiko Usuda; Daiki Mori; Hiromitsu Haba; Hirofumi Fujii; Masahiro Yasunaga; Yasuhiro Matsumura

doi:10.1021/acsomega.1c00684

Stabilization of an ²¹¹At-Labeled Antibody with Sodium Ascorbate

ACS Omega. 2021 May 31;6(23):14887-14895. doi: 10.1021/acsomega.1c00684. eCollection 2021 Jun 15.

Authors

Shino Manabe^{1

2

3}, Hiroki Takashima⁴, Kazunobu Ohnuki⁵, Yoshikatsu Koga^{4

6}, Ryo Tsumura⁴, Nozomi Iwata⁴, Yang Wang⁷, Takuya Yokokita⁷, Yukiko Komori⁷, Sachiko Usuda⁷, Daiki Mori⁷, Hiromitsu Haba⁷, Hirofumi Fujii⁵, Masahiro Yasunaga⁴, Yasuhiro Matsumura⁸

Affiliations

¹ Pharmaceutical Department, Hoshi University 2-4-41, Ebara, Shinagawa, Tokyo 142-8501, Japan.
² Research Center for Pharmaceutical Development Graduate School of Pharmaceutical Sciences & Faculty of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
³ Glycometabolic Biochemistry Laboratory, RIKEN, Hirosawa, Wako, Saitama 351-0198, Japan.
⁴ Division of Developmental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 6-5-1 Kahiwanoha, Kashiwa City 277-8577, Japan.
⁵ Division of Functional Imaging, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 6-5-1 Kahiwanoha, Kashiwa City 277-8577, Japan.
⁶ Department of Strategic Programs, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, 6-5-1 Kahiwanoha, Kashiwa City 277-8577, Japan.
⁷ Nishina Center for Accelerator-Based Science, RIKEN, Hirosawa, Wako-shi, Saitama 351-0198 Japan.
⁸ Department of Immune Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, 104-0045 Tokyo, Japan.

Abstract

²¹¹At, an α-particle emitter, has recently attracted attention for radioimmunotherapy of intractable cancers. However, our sodium dodecyl sulfate polyacrylamide gel electrophoresis and flow cytometry analyses revealed that ²¹¹At-labeled immunoconjugates are easily disrupted. Luminol assay revealed that reactive oxygen species generated from radiolysis of water caused the disruption of ²¹¹At-labeled immunoconjugates. To retain their functions, we explored methods to protect ²¹¹At-immunoconjugates from oxidation and enhance their stability. Among several other reducing agents, sodium ascorbate most safely and successfully protected ²¹¹At-labeled trastuzumab from oxidative stress and retained the stability of the ²¹¹At-labeled antibody and its cytotoxicity against antigen-expressing cells for several days.