Azido 18F-arenes are important and versatile building blocks for radiolabeling of biomolecules via Huisgen cycloaddition (‘click chemistry’) in positron emission tomography (PET). However, routine access of such clickable agents is challenged by inefficient multi-step and esoteric radiochemical approaches. Herein we describe a high-yielding direct radiofluorination for azido 18F-arenes by developing an oxygen ortho-stabilized iodonium derivative (OID). This OID strategy addresses an unmet need for a reliable azido 18F-arene clickable agent in bioconjugation reactions. A ssDNA aptamer is radiolabeled and visualized in a xenograft mouse model of human colon cancer by PET, which demonstrates a convenient and highly efficient way of labeling biomolecules and tracking them by OID approach.

Azido 18 F-arenes are important and versatile building blocks for the radiolabeling of biomolecules via Huisgen cycloaddition ("clickc hemistry") for positron emission tomography (PET). However,r outine access to such clickable agents is challenged by inefficient and/or poorly defined multistep radiochemical approaches.Ahigh-yielding direct radiofluorination for azido 18 F-arenes was achieved through the development of an ortho-oxygen-stabilizedi odonium derivative (OID). This OID strategy addresses an unmet need for ar eliable azido 18 F-arene clickable agent for bioconjugation reactions.AssDNAaptamer was radiolabeled with this agent and visualizedi naxenograft mouse model of human colon cancer by PET,w hichd emonstrates that this OID approach is ac onvenient and highly efficient way of labeling and trackingbiomolecules.