18F-Trifluoromethanesulfinate Enables Direct C-H 18F-Trifluoromethylation of Native Aromatic Residues in Peptides.
Kee CW., Tack O., Guibbal F., Wilson TC., Isenegger PG., Imiołek M., Verhoog S., Tilby M., Boscutti G., Ashworth S., Chupin J., Kashani R., Poh AWJ., Sosabowski JK., Macholl S., Plisson C., Cornelissen B., Willis MC., Passchier J., Davis BG., Gouverneur V.
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.