Open AccessStabilization of an 211At-Labeled Antibody with Sodium Ascorbate
Author(s) -
Shino Manabe,
Hiroki Takashima,
Kazunobu Ohnuki,
Yoshikatsu Koga,
Ryo Tsumura,
Nozomi Iwata,
Yan Wang,
Takuya Yokokita,
Yukiko Komori,
Sachiko Usuda,
Daisuke Mori,
Hiromitsu Haba,
Hirofumi Fujii,
Masahiro Yasunaga,
Yasuhiro Matsumura
Publication year - 2021
Publication title -
acs omega
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.779
H-Index - 40
ISSN - 2470-1343
DOI - 10.1021/acsomega.1c00684
Subject(s) - chemistry , sodium ascorbate , reactive oxygen species , flow cytometry , sodium dodecyl sulfate , cytotoxicity , biochemistry , chromatography , ascorbic acid , microbiology and biotechnology , biology , food science , in vitro
211 At, 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 211 At-labeled immunoconjugates are easily disrupted. Luminol assay revealed that reactive oxygen species generated from radiolysis of water caused the disruption of 211 At-labeled immunoconjugates. To retain their functions, we explored methods to protect 211 At-immunoconjugates from oxidation and enhance their stability. Among several other reducing agents, sodium ascorbate most safely and successfully protected 211 At-labeled trastuzumab from oxidative stress and retained the stability of the 211 At-labeled antibody and its cytotoxicity against antigen-expressing cells for several days.