Detecting hypoxia using 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 F-tetrazine probe ([F]FB-Tz) and 2-nitroimidazole-based TCO targeting molecule () showed statistically significant ( < 0.0001) uptake in hypoxic cells ( 90 %ID per mg) normoxic cells (<10 %ID per mg) in a 60 min incubation of [F]FB-Tz.