Post-radiolabeling thioether oxidation to enhance the bioorthogonal reactivity of 18F-tetrazines

Abstract

Radiolabeled 1,2,4,5-tetrazines are powerful heterocyclic agents for bioorthogonal PET imaging due to their fast cycloaddition with trans-cyclooctenes. However, fluorine-18 radiolabeling of highly reactive tetrazines is often not feasible due to limited compound stability. We demonstrate that post-radiolabeling oxidation of thioether functionalities is a viable and transferable strategy to avoid these limitations, enabling the synthesis of highly reactive 18F-tetrazines. Graphical abstract: [Figure not available: see fulltext.].