Site-Selective, Late-Stage C-H ¹⁸ F-Fluorination on Unprotected Peptides for Positron Emission Tomography Imaging

Peptides are often ideal ligands for diagnostic molecular imaging due to their ease of synthesis and tuneable targeting properties. However, labelling unmodified peptides with ¹⁸ F for positron emission tomography (PET) imaging presents a number of challenges. Here we show the combination of photoactivated sodium decatungstate and [¹⁸ F]-N-fluorobenzenesulfonimide effects site-selective ¹⁸ F-fluorination at the branched position in leucine residues in unprotected and unaltered peptides. This streamlined process provides a means to directly convert native peptides into PET imaging agents under mild aqueous conditions, enabling rapid discovery and development of peptide-based molecular imaging tools.