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

RSC Adv. 2021 Jun 7;11(33):20335-20341. doi: 10.1039/d1ra02482e.

Authors

Louis Allott^{1

2}, Cen Chen¹, Marta Braga¹, Sau Fung Jacob Leung¹, Ning Wang¹, Chris Barnes¹, Diana Brickute¹, Laurence Carroll^{1

3}, Eric O Aboagye¹

Affiliations

¹ Comprehensive Cancer Imaging Centre, Faculty of Medicine, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Du Cane Road London W12 0NN UK eric.aboagye@imperial.ac.uk.
² Positron Emission Tomography Research Centre, Faculty of Health Sciences, University of Hull Cottingham Road Kingston upon Hull HU6 7RX UK.
³ Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Medical Institutions Baltimore Maryland USA.

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.