Detecting hypoxia: In vitro using 18F-pretargeted IEDDA "click" chemistry in live cells

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

doi:10.1039/d1ra02482e

Detecting hypoxia: In vitro using ¹⁸F-pretargeted IEDDA "click" chemistry in live cells

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	20335-20341
Number of pages	7
Journal	RSC Advances
Volume	11
Issue number	33
DOIs	https://doi.org/10.1039/d1ra02482e
State	Published - Jun 7 2021

ASJC Scopus subject areas

General Chemistry
General Chemical Engineering

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10.1039/d1ra02482e

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AU - Allott, Louis

AU - Chen, Cen

AU - Braga, Marta

AU - Leung, Sau Fung Jacob

AU - Wang, Ning

AU - Barnes, Chris

AU - Brickute, Diana

AU - Carroll, Laurence

AU - Aboagye, Eric O.

PY - 2021/6/7

Y1 - 2021/6/7

N2 - 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.

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Detecting hypoxia: In vitro using ¹⁸F-pretargeted IEDDA "click" chemistry in live cells

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