Stabilization of an 211At-Labeled Antibody with Sodium Ascorbate.
Shino ManabeHiroki TakashimaKazunobu OhnukiYoshikatsu KogaRyo TsumuraNozomi IwataYang WangTakuya YokokitaYukiko KomoriSachiko UsudaDaiki MoriHiromitsu HabaHirofumi FujiiMasahiro YasunagaYasuhiro MatsumuraPublished in: ACS omega (2021)
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.
Keyphrases
- pet imaging
- flow cytometry
- oxidative stress
- induced apoptosis
- reactive oxygen species
- single cell
- high throughput
- cell proliferation
- ischemia reperfusion injury
- epidermal growth factor receptor
- computed tomography
- cell cycle arrest
- young adults
- nitric oxide
- signaling pathway
- endoplasmic reticulum stress
- cell death
- hyaluronic acid