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Fluorine-18 labeled biomolecules such as peptides, proteins or polysaccharides are valuable tools for molecular imaging by positron emission tomography (PET), but their radiolabeling remains a challenge. Indeed, the drastic conditions (high temperatures or non-aqueous conditions) necessary for radiofluorination are not compatible with the complexity and fragility of these compounds. To address these issues, two-step strategies have been developed : they involve the preparation of a fluorine-18 labeled prosthetic compound which is then conjugated to the biomolecule of interest under biocompatible conditions.

In this study, the researchers designed, synthesized, and radiolabeled a novel fluoropyridine thiol, [¹⁸F]FPySH, in a fully automated manner and with good radiochemical yield. They then conjugated it onto model biomolecules containing either : a) a dehydroalanine (dha) motif, an unsaturated amino acid obtained from a native cysteine or b) a maleimide function, an α, β-unsaturated carbonyl that is highly reactive toward various nucleophiles. In both cases, the conjugation of the prosthetic thiol group on the dha or maleimide motifs takes place via a Michael addition. Conjugation of [¹⁸F]FPySH to a template molecule and a glutathione analog with the dha motif was achieved in 30-45 min, whereas radiolabeling of the maleimide-modified c(RGDfK) peptide yielded the radiofluorinated analog in 15 min. These times are both compatible with the half-life of fluor-18.

The authors are currently working on the implementation of this original technique for the labeling of more complex biomolecules such as proteins.

Contacts : Mylène Richard (mylene.richard@cea.fr) ; Bertrand Kuhnast (bertrand.kuhnast@cea.fr)