Synthesis and application of [18F]FDG-maleimidehexyloxime ([18F]FDG-MHO): a [18F]FDG-based prosthetic group for the chemoselective 18F-labeling of peptides and proteins

2-(18)F]Fluoro-2-deoxy-D-glucose ((18)F]FDG) as the most important PET radiotracer is available in almost every PET center. However, there are only very few examples using (18)F]FDG as a building block for the synthesis of (18)F-labeled compounds. The present study describes the use of (18)F]FDG as a building block for the synthesis of (18)F-labeled peptides and proteins. (18)F]FDG was converted into (18)F]FDG-maleimidehexyloxime ((18)F]FDG-MHO), a novel (18)F]FDG-based prosthetic group for the mild and thiol group-specific (18)F labeling of peptides and proteins. The reaction was performed at 100 degrees C for 15 min in a sealed vial containing (18)F]FDG and N-(6-aminoxy-hexyl)maleimide in 80% ethanol. (18)F]FDG-MHO was obtained in 45-69% radiochemical yield (based upon (18)F]FDG) after HPLC purification in a total synthesis time of 45 min. Chemoselecetive conjugation of (18)F]FDG-MHO to thiol groups was investigated by the reaction with the tripeptide glutathione (GSH) and the single cysteine containing protein annexin A5 (anxA5). Radiolabeled annexin A5 ((18)F]FDG-MHO-anxA5) was obtained in 43-58% radiochemical yield (based upon (18)F]FDG-MHO, n = 6), and (18)F]FDG-MHO-anxA5 was used for a pilot small animal PET study to assess in vivo biodistribution and kinetics in a HT-29 murine xenograft model.