Radiofluorination and first radiopharmacological characterization of a SWLAY peptide-based ligand targeting EphA2

Peptides labeled with short-lived positron-emitting radionuclides are of considerable interest as probes for molecular imaging by positron emission tomography (PET). Herein, the regioselective and convenient radiofluorination of a biologically relevant alkyne-modified SWLAY peptide bound on solid support with the radiolabeling building block 1-(3-azidopropyl)-4-(3-fluoropropyl)piperazine ([¹⁸F]AFP) is described.
The desired ¹⁸F-peptide could be prepared in a total synthesis time of 140 min including the removal of the catalytic copper species and was obtained with a RCY of 7–13% and a RCP > 98%. The method’s feasibility for a robust and bioorthogonal radiolabeling via the 1,3-dipolar Huisgen cycloaddition was demonstrated. Preliminary radiopharmacological studies regarding the metabolic stability of the peptides in cell culture supernatants and rat plasma were accomplished as well as the cellular association of the ¹⁸F-peptide in EphA2-overexpressing human melanoma cells in vitro. Furthermore, an initial in vivo PET experiment was performed which showed a fast metabolism of the novel ¹⁸F-peptide followed by an accumulation in the kidneys, followed by elimination into the bladder.