2-Fluoropyridine prosthetic compounds for the 18F labeling of bombesin analogues

Acetylene-bearing 2-[18F]fluoropyridines [18F]FPy5yne and PEG-[18F]FPyKYNE were prepared via efficient nucleophilic heteroaromatic [18F]fluorination of their corresponding 2-trimethylammoniumpyrdinyl precursors. The prosthetic groups were conjugated to azide- and PEG3-modified bombesin(6-14) analogues via copper-catalyzed azide-alkyne cycloaddition couplings to yield mono- and di-mini-PEGylated ligands for PET imaging of the gastrin- releasing peptide receptor. The PEG3- and PEG2/PEG3-bearing 18F peptides showed decreased lipophilicity relative to an analogous non-mini-PEGylated 18F peptide. Assessment of water-soluble peptide pharmacokinetics and tumour-targeting capabilities in a mouse model of prostate cancer is currently underway.