title: Radiofluorination and first radiopharmacological characterization of a SWLAY peptide-based ligand targeting EphA2.
abstract: Peptides labeled with short-lived positron emitters are of considerable interest as probes for molecular imaging by positron emission tomography. 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 ([(18) F]AFP) is described. Peptides including this amino acid sequence are promising candidates for imaging of the erythropoietin-producing hepatoma cell line-A2 receptor (Eph), which is an interesting target for tumor imaging due to its overexpression in various tumor entities. The desired (18) F-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 radiochemical yield of 11 ± 2% (n = 5) and a radiochemical purity >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 (18) F-peptide in erythropoietin-producing hepatoma cell line-A2-overexpressing human melanoma cells in vitro. Furthermore, an initial in vivo positron emission tomography experiment was performed, which showed a fast metabolism of the novel (18) F-peptide.
authors.affiliation: Institut für Radiopharmazeutische Krebsforschung, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, D-01328, Dresden, Germany; Fachbereich Chemie und Lebensmittelchemie, Technische Universität Dresden, D-01062, Dresden, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Pretze
authors.forename: Birgit
authors.initials: B
authors.lastname: Mosch
authors.forename: Ralf
authors.initials: R
authors.lastname: Bergmann
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
authors.forename: Constantin
authors.initials: C
authors.lastname: Mamat
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000138:chemical synthesis / Q000493:pharmacokinetics; D010879:Piperazines / Q000138:chemical synthesis / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D036104:Receptor, EphA2 / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D009842:Oligopeptides; D010879:Piperazines; D019275:Radiopharmaceuticals; D036104:Receptor, EphA2
keywords: EphA2 ligand; Huisgen click; bioorthogonal; solid phase peptide synthesis