title: Synthesis of a non-peptidic PET tracer designed for α5β1 integrin receptor.
abstract: Arginine-glycine-aspartic acid (RGD)-containing peptides have been traditionally used as PET probes to noninvasively image angiogenesis, but recently, small selective molecules for α5 β1 integrin receptor have been developed with promising results. Sixty-one antagonists were screened, and tert-butyl (S)-3-(2-((3R,5S)-1-(3-(1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)propanoyl)-5-((pyridin-2-ylamino)methyl)pyrrolidin-3-yloxy)acetamido)-2-(2,4,6-trimethylbenzamido)propanoate (FPMt) was selected for the development of a PET tracer to image the expression of α5 β1 integrin receptors. An alkynyl precursor (PMt) was initially synthesized in six steps, and its radiolabeling was performed according to the azide-alkyne copper(II)-catalyzed Huisgen's cycloaddition by using 1-azido-2-[(18)F]fluoroethane ([(18)F]12). Different reaction conditions between PMt and [(18)F]12 were investigated, but all of them afforded [(18)F]FPMt in 15 min with similar radiochemical yields (80-83%, decay corrected). Overall, the final radiopharmaceutical ([(18)F]FPMt) was obtained after a synthesis time of 60-70 min in 42-44% decay-corrected radiochemical yield.
authors.affiliation: Cyclotron Unit, University Hospital of Geneva, Rue Gabrielle Perret-Gentil 4, 1211, Geneva, Switzerland; School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, Quai Ernest Ansermet 30, 1211, Geneva, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Monaco
authors.forename: Olivier
authors.initials: O
authors.lastname: Michelin
authors.forename: John
authors.initials: J
authors.lastname: Prior
authors.forename: Curzio
authors.initials: C
authors.lastname: Rüegg
authors.forename: Leonardo
authors.initials: L
authors.lastname: Scapozza
authors.forename: Yann
authors.initials: Y
authors.lastname: Seimbille
mesh_terms: D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007553:Isotope Labeling; D009842:Oligopeptides / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics
chemical_list: D005462:Fluorine Radioisotopes; D039081:Integrin alpha5beta1; D009842:Oligopeptides; D019275:Radiopharmaceuticals; C047981:arginyl-glycyl-aspartic acid
keywords: PET, 1-azide-2-[18F]fluoroethane; click chemistry; peptido-mimetic; α5β1 integrin receptor