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

Allott, Louis; Chen, Cen; Braga, Marta; Leung, Sau Fung Jacob; Wang, Ning; Barnes, Chris; Brickute, Diana; Carroll, Laurence; Aboagye, Eric O.

Abstract

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 18F-tetrazine probe ([18F]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 [18F]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.

Citation

Allott, L., Chen, C., Braga, M., Leung, S. F. J., Wang, N., Barnes, C., …Aboagye, E. O. (in press). Detecting hypoxia in vitro using 18F-pretargeted IEDDA “click” chemistry in live cells. RSC advances, 11(33), 20335-20341. https://doi.org/10.1039/d1ra02482e

• Journal Article Type: Article
• Acceptance Date: Jun 1, 2021
• Online Publication Date: Jun 7, 2021
• Deposit Date: Jun 7, 2021
• Publicly Available Date: Oct 27, 2022
• Journal: RSC Advances
• Print ISSN: 2046-2069
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 33
• Pages: 20335-20341
• DOI: https://doi.org/10.1039/d1ra02482e
• Keywords: General Chemistry; General Chemical Engineering
• Public URL: https://hull-repository.worktribe.com/output/3786690