¹⁸F-Trifluoromethanesulfinate Enables Direct C–H ¹⁸F-Trifluoromethylation of Native Aromatic Residues in Peptides

Abstract

¹⁸F labeling strategies for unmodified peptides with [¹⁸F]fluoride require ¹⁸F-labeled prosthetics for bioconjugation more often with cysteine thiols or lysine amines. Here we explore selective radical chemistry to target aromatic residues applying C-H ¹⁸F-trifluoromethylation. We report a one-step route to [¹⁸F]CF₃SO₂NH₄ from [¹⁸F]fluoride and its application to direct [¹⁸F]CF₃ incorporation at tryptophan or tyrosine residues using unmodified peptides as complex as recombinant human insulin. The fully automated radiosynthesis of octreotide[Trp(2-CF₂¹⁸F)] enables in vivo positron emission tomography imaging.