Looking for New [1,2,4,5]Tetrazines to Produce 99mTc‐Labelled Derivatives, with a Suitable Lipophilicity Balance for Use in Bioorthogonal Reactions

The reaction between [1,2,4,5]tetrazines with trans‐cyclooctene through the cycloaddition process has been described as a powerful tool in bioorthogonal processes. Specifically the diagnostic with fluorescent‐ and radio‐labelled [1,2,4,5]tetrazines and pre‐targeted trans‐cyclooctene modified‐antibod...

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Bibliographic Details
Published in:ChemistrySelect (Weinheim) 2023-11, Vol.8 (41), p.n/a
Main Authors: Rodríguez, Gonzalo, Fernández, Marcelo, Cabrera, Mirel, Tassano, Marcos, Cabral, Pablo, Couto, Marcos, Cerecetto, Hugo, García., María Fernanda
Format: Article
Language:English
Subjects:
chelator
click chemistry
cyclam
DTPA
technetium
tetrazine
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Summary:The reaction between [1,2,4,5]tetrazines with trans‐cyclooctene through the cycloaddition process has been described as a powerful tool in bioorthogonal processes. Specifically the diagnostic with fluorescent‐ and radio‐labelled [1,2,4,5]tetrazines and pre‐targeted trans‐cyclooctene modified‐antibody has been used by us for this purpose. Our previously developed 99mTc‐radiolabelled [1,2,4,5]tetrazine‐derivatives porting 6‐hydrazinonicotinyl‐chelator displayed some limitations related to its unappropriated biodisposal. Herein, we explored [1,2,4,5]tetrazines porting other 99mTc‐coordination‐moieties, 1,4,8,11‐tetrazacyclotetradecanyl and diethylenetriaminepentaacetyl, as potential hydrophilic functions. Some of the new modified [1,2,4,5]tetrazines were able to coordinate efficiently the radionuclide generating 99mTc‐counterparts that reacted with trans‐cyclooctene modified‐bevacizumab and recognized cells that overexpress vascular endothelial growth factor (VEGF). Additionally, the in vivo 99mTc‐counterparts‐biodistributions were studied, on the desired organs, and they resulted dependent of lipophilicity. In this work, the development and study of new [1,2,4,5]tetrazines to be coordinated with the radionuclide 99mTc and further used in biorthogonal processes was described. The design strategy was based on the modification of the lipophilicity of these bioorthogonal‐counterparts. The obtained compounds displayed interesting in vivo behaviour which will enable further structural‐designs.
ISSN:2365-6549
2365-6549
DOI:10.1002/slct.202302961