Fig. 1

Conceptual representation of a two-step pretargeted method based on IEDDA reaction. The current approach involves the sequential administration of an antibody, followed by administration of a small molecule radiotracer after 24–72 h. a TCO-modified antibody is administered first. It circulates for a couple of days and eventually accumulates in the tumour and clears from the blood pool and other non-target tissues. b After a predetermined lag time, a radiolabelled tetrazine tracer is administered. It reacts selectively with the TCO group attached to the antibody and the unreacted tracer clears rapidly from the blood. In this work, the used radiotracer was ¹⁸F-labelled tetrazine, [¹⁸F]TAF. c The antibody can now be localized via the radiolabel on the tracer. The pretargeting approach with short-lived tracer significantly lowers the radiation burden to the subject compared to traditional methods where the antibody is directly radiolabelled with a longer-lived radionuclide