Radiosynthesis and bioconjugation of [18F]FPy5yne, a prosthetic group for the 18F labeling of bioactive peptides

A new 18F‐based prosthetic group has been prepared for the labeling of azide‐modified peptides for use in PET imaging. 2‐[18F]fluoro‐3‐(hex‐5‐ynyloxy)pyridine ([18F]FPy5yne, [18F]‐1) was prepared via efficient nucleophilic heteroaromatic substitution of either the corresponding 2‐nitro (2) or 2‐trimethylammonium trifluoromethanesulfonate pyridine (3). Best radiochemical yield of [18F]FPy5yne from 2 was 91% by radioTLC (15 min, 110°C, DMSO). From 3, best radiochemical yield by radioTLC was 93% (15 min, 110°C, MeCN). HPLC‐purified [18F]FPy5yne was ligated to model peptide N3–(CH2)4–CO–YKRI–OH by way of CuI‐mediated Huisgen [3+2] cycloaddition in the presence of copper‐stabilizing ligand tris(benzyltriazolylmethyl)amine (TBTA) and N,N‐diisopropylethylamine (DIEA). Bioconjugate radiochemical yields were obtained in average yields of 89%±8.6% (n=4), as judged by radioHPLC. Best non‐decay‐corrected, collected radiochemical yield of modified peptide from end‐of‐bombardment was 5.8% (18.7% decay‐corrected), with a total preparation time of 160 min from start of synthesis. Copyright © 2008 John Wiley & Sons, Ltd. 2‐[18F]fluoro‐3‐(hex‐5‐ynyloxy)pyridine ([18F]FPy5yne) was prepared via efficient nucleophilic heteroaromatic [18F]flurorination and ligated to a model 4‐amino acid peptide by way of CuI‐ mediated Huisgen [3+2] cycloaddition. Copyright © 2008 John Wiley & Sons, Ltd.