Trans-Cyclooctene Isomerization Catalyzed by Thiamine Degradation Products in Cell Culture Media
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Le résumé fourni par la source
High Resolution Image Download MS PowerPoint Slide PET imaging of intrathecally dosed ASO neurology drugs is challenging due to the long time needed to achieve steady-state brain distribution, making the use of a simple 18 F tag impossible with its short radioactive half-life. To overcome this challenge, a pretargeted imaging solution has been developed in which an ASO tagged with a tetrazine is dosed intrathecally, and after 24 h a reactive trans -cyclooctene (TCO) tagged with 18 F is dosed intravenously. The two molecules form a click-chemistry adduct, allowing for PET imaging scans immediately following 18 F-TCO administration. Although it has been demonstrated that TCOs can be relatively stable in vivo, they rapidly isomerize to cis -cyclooctenes (CCOs) in cell culture media and “aged” plasma, making many DMPK experiments challenging to interpret and not representative of the in vivo stability. The predominant cause of isomerization was determined to be thiamine degradation product(s) in media such as DMEM. Several techniques to overcome the challenges of in vitro and ex vivo isomerization during analytical experiments are herein proposed, such as the use of custom media and/or fresh plasma, adding antioxidants, using surrogate molecules, and using TCO trapping agents. These findings and techniques may also be relevant to other applications in which TCOs are incubated in thiamine-containing cell culture media.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- <i>Trans</i>-Cyclooctene Isomerization Catalyzed by Thiamine Degradation Products in Cell Culture Media
- Date Crossref
- 05/06/2025
- Éditeur
- American Chemical Society (ACS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Biogen (United States) pays non établi dans la noticeEntreprise
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Biomark (United States) pays non établi dans la noticeEntreprise
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Biogen (Switzerland) pays non établi dans la noticeEntreprise
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Drug Metabolism and Pharmacokinetics pays non établi dans la noticeInstitution
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ASO Development pays non établi dans la noticeInstitution
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Medicinal Chemistry pays non établi dans la noticeInstitution
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Biomarkers pays non établi dans la noticeInstitution
Biogen (United States), Biomark (United States) et Biogen (Switzerland), avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.