A Compact and Synthetically Accessible Fluorine‐18 Labelled Cyclooctyne Prosthetic Group for Labelling of Biomolecules by Copper‐Free Click Chemistry

Abstract

Abstract A new fluorine‐containing azadibenzocyclooctyne (ADIBO‐F) was designed using a synthetically accessible pathway. The fluorine‐18 prosthetic group was prepared from its toluenesulfonate precursor and isolated in 21–35 % radiochemical yield in 30 minutes of synthetic time. ADIBO‐F has been incorporated into azide‐functionalized, cancer‐targeting peptides through a strain‐promoted alkyne–azide cycloaddition with high radiochemical yields and purities. The final products are novel peptide‐based positron emission tomography (PET) imaging agents that possess high affinities for their targets, growth hormone secretagogue receptor 1a (GHSR‐1a) and gastrin‐releasing peptide receptor (GRPR), with IC 50 values of 9.7 and 0.50 n m , respectively. This is a new and rapid labelling option for the incorporation of fluorine‐18 into biomolecules for PET imaging.