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.
Wuest
Frank
F
Research Center Dresden-Rossendorf, Institute for Radiopharmacy, PF 510 119, D-01314 Dresden, Germany. f.wuest@fzd.de
Berndt
Mathias
M
Bergmann
Ralf
R
van den Hoff
Joerg
J
Pietzsch
Jens
J
D000818:Animals; D017304:Annexin A5 / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D005240:Feasibility Studies; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007700:Kinetics; D008301:Maleimides / Q000138:chemical synthesis* / Q000737:chemistry; D051379:Mice; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D049268:Positron-Emission Tomography; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D013194:Staining and Labeling / Q000379:methods*; D013379:Substrate Specificity; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D017304:Annexin A5; D005462:Fluorine Radioisotopes; D008301:Maleimides; D010091:Oximes; D010455:Peptides; D011506:Proteins; D013438:Sulfhydryl Compounds; C530255:fluorodeoxyglucose F18-maleimidehexyloxime; D019788:Fluorodeoxyglucose F18; D005978:Glutathione