Synthical logo
Synthical
Your space
Profile
Activity
Favorites
Folders
Feeds

Resin-assisted synthesis of a neopentyl 211At-labeled activated ester possessing a triazole spacer and its application to the synthesis of in vivo stable 211At-labeled antibodies.

In this study we developed a neopentyl 211At-labeled activated ester that incorporates a triazole spacer and applied it to the synthesis of an 211At-labeled cetuximab. The activated ester was synthesized via the nucleophilic 211At-astatination of a neopentyl sulfonate carrying two long alkyl chains that serve as a lipid tag, which was followed by the hydrolysis of an acetal. The triazole spacer significantly enhanced the reactivity of the neopentyl sulfonate towards nucleophilic substitution. Additionally, we developed a novel Resin-Assisted Purification and Deprotection (RAPD) protocol involving a solid-phase extraction of the protected 211At-labeled compound from the mixture of the labeling reaction, hydrolysis of the acetal on the resin, and finally an elution of the 211At-labeled activator from the resin. This method allows the synthesis of an 211At-labeled activated ester with high purity through a simplified procedure that circumvents the need for HPLC purification. Using this 211At-labeled activated ester, we efficiently synthesized 211At-labeled cetuximab in 27±1% radiochemical yield with 95% radiochemical purity. This activated ester demonstrated high reactivity, and enabled the completion of the reaction with the antibody within 10 minutes. In comparative biodistribution studies between 211At-labeled cetuximab and the corresponding 125I-labeled cetuximab in normal mice, we observed equivalent radioactivity distribution after administration, and both the thyroid and stomach showed radioactivity levels that were less than 1.0% of the injected dose. These findings indicate a suppressed dehalogenation of the 211At-labeled cetuximab, which emphasizes the effectiveness of the 211At-labeled activated ester.
Simplify
Published on April 2, 2024
Copy BibTeX
Loading PDF…
Loading...
Comments
Summary
There is no AI-powered summary yet, because we do not have a budget to generate summaries for all articles.
1. Buy subscription
We will thank you for helping thousands of people to save their time at the top of the generated summary.
If you buy our subscription, you will be able to summarize multiple articles.
Pay $undefined
≈10 summaries
Pay $undefined
≈60 summaries
2. Share on socials
If this article gets to top-5 in trends, we'll summarize it for free.
Copy link
Content
Summary