Detecting hypoxia in vitro using (18)F-pretargeted IEDDA “click” chemistry in live cells

We have exemplified a pretargeted approach to interrogate hypoxia in live cells using radioactive bioorthogonal inverse electron demand Diels–Alder (IEDDA) “click” chemistry. Our novel (18)F-tetrazine probe ([(18)F]FB-Tz) and 2-nitroimidazole-based TCO targeting molecule (8) showed statistically sig...

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Detalles Bibliográficos
Autores principales: Allott, Louis, Chen, Cen, Braga, Marta, Leung, Sau Fung Jacob, Wang, Ning, Barnes, Chris, Brickute, Diana, Carroll, Laurence, Aboagye, Eric O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182949/
https://www.ncbi.nlm.nih.gov/pubmed/34178309
http://dx.doi.org/10.1039/d1ra02482e
Descripción
Sumario:We have exemplified a pretargeted approach to interrogate hypoxia in live cells using radioactive bioorthogonal inverse electron demand Diels–Alder (IEDDA) “click” chemistry. Our novel (18)F-tetrazine probe ([(18)F]FB-Tz) and 2-nitroimidazole-based TCO targeting molecule (8) showed statistically significant (P < 0.0001) uptake in hypoxic cells (ca. 90 %ID per mg) vs. normoxic cells (<10 %ID per mg) in a 60 min incubation of [(18)F]FB-Tz. This is the first time that an intracellularly targeted small-molecule for IEDDA “click” has been used in conjunction with a radioactive reporter molecule in live cells and may be a useful tool with far-reaching applicability for a variety of applications.

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