A novel role for [18F]FDG: Synthesis and application of a [18F]FDG-based prosthetic group for peptide and protein labeling


A novel role for [18F]FDG: Synthesis and application of a [18F]FDG-based prosthetic group for peptide and protein labeling

Berndt, M.; Pietzsch, J.; Bergmann, R.; Wüst, F.

Objectives: The routine 18F labeling of biomacromolecules like peptides and proteins should involve simple and efficient radiolabeling methods based on readily available prosthetic groups. 2-[18F]Fluoro-2-deoxy-D-glucose ([18F]FDG) as the most important PET radiotracer is available in almost every PET center. However, there are only very few examples using [18F]FDG as a building block for the radiosynthesis of 18F-labeled compounds.
The present study describes the use of [18F]FDG as a 18F building block for the convenient single-step synthesis of thiol-reactive prosthetic group [18F]FDG-maleimidehexyloxime ([18F]FDG-MHO). The potential of this novel [18F]FDG-based prosthetic group was evaluated by the reaction with thiol group-containing biomacro-molecules.

Methods: The reaction was performed using a 0.9% NaCl solution of [18F]FDG and N-(6-aminoxyhexyl)maleimide in 80% ethanol. The mixture was heated at 100°C in a sealed vial for 15 min. Then, ethanol was evaporated and [18F]FDG-MHO was purified by HPLC. Conjugation of [18F]FDG-MHO to thiol groups was investigated by the reaction with the tripeptide glutathione and the protein Annexin-V.

Results: [18F]FDG-MHO was obtained in 45-69 % radiochemical yield after HPLC purification in a total synthesis time of 50 min. The use of [18F]FDG-MHO as a selective thiol-reactive reagent was first exemplified using various concentrations of glutathione. The reaction was monitored by radio-TLC. At glutathione concentrations ranging from 30 µmol to <100 pmol we found complete consumption of the labeling agent. The application of [18F]FDG-MHO was further investigated by the conjugation to Annexin-V that contains one accessible cysteine side chain. Radiolabeling yields of up to 80% (based upon [18F]FDG-MHO) could be achieved.

Conclusion: The thiol-reactive prosthetic group [18F]FDG-MHO derived from readily available [18F]FDG has been developed. The labeling experiments using glutathione as a model peptide and Annexin-V as protein indicate that [18F]FDG-MHO can be used for the mild and selective 18F labeling of thiol group-containing biomacro-molecules like peptides and proteins.

  • Abstract in refereed journal
    Journal of Nuclear Medicine 47(2006)Suppl. 1, 29P
  • Lecture (Conference)
    53rd Annual Meeting of the Society of Nuclear Medicine, 03.-07.06.2006, San Diego, USA

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Publ.-Id: 7981