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

2-[F-18]Fluoro-2-deoxy-D-glucose ([F-18]FDG) as the most important PET radiotracer is available in almost every PET center. However, there are only very few examples using [F-18]FDG as a building block for the synthesis of 18 F-labeled compounds. The present study describes the use of [F-18]FDG as a building block for the synthesis of F-18-labeled peptides and proteins. [F-18]FDG was converted into [F-18]FDG-maleimidehexyloxime ([F-18]FDG-MHO), a novel [F-18]FDG-based prosthetic group for the mild and thiol group-specific F-18 labeling of peptides and proteins. The reaction was performed at 100 degrees C for 15 min in a sealed via] containing [F-18]FDG and N-(6-aminoxy-hexyl)maleimide in 80% ethanol. [v]FDG-MHO was obtained in 45-69% radiochemical yield (based upon [F-18]FDG) after HPLC purification in a total synthesis time of 45 min. Chemoselecetive conjugation of F-18]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 ([F-18]FDG-MHO-anxA5) was obtained in 43-58% radiochemical yield (based upon [F-18]FDG-MHO, n = 6), and [F-18]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.