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

A new 18 F‐based prosthetic group has been prepared for the labeling of azide‐modified peptides for use in PET imaging. 2‐[ 18 F]fluoro‐3‐(hex‐5‐ynyloxy)pyridine ([ 18 F]FPy5yne, [ 18 F]‐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 [ 18 F]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 [ 18 F]FPy5yne was ligated to model peptide N 3 –(CH 2 ) 4 –CO–YKRI–OH by way of Cu I ‐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.