title: Synthesis and in vitro evaluation of small-molecule [18F] labeled gonadotropin-releasing hormone (GnRH) receptor antagonists as potential PET imaging agents for GnRH receptor expression.
abstract: Two novel small molecule gonadotropin-releasing hormone (GnRH) receptor antagonists (12 and 13) of the furamide-class were synthesized and evaluated in vitro for their receptor binding affinities for the rat GnRH receptor. Radiolabeling with no carrier added fluorine-18 of the appropriate precursors was investigated in a one-step reaction. LogP (Octanol/PBS pH 7.4) and serum stability of the compounds were investigated. The antagonists showed low nM affinity for the rat GnRH receptor. (18)F-radiolabled compounds were obtained in high radiochemical purity (>95%) and specific activity (>75 GBq/μmol). These findings suggest this class of compounds holds promise as potential probes for PET targeting of GnRH-receptor expression.
authors.affiliation: Norwegian Medical Cyclotron Centre, PO Box 4950, Nydalen, N-0424 Oslo, Norway.
authors.forename: Dag Erlend
authors.initials: DE
authors.lastname: Olberg
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Oslo, Norway.
authors.forename: Kjetil Wessel
authors.initials: KW
authors.lastname: Andressen
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Oslo, Norway.
authors.forename: Finn Olav
authors.initials: FO
authors.lastname: Levy
authors.affiliation: School of Pharmacy, University of Oslo, Norway.
authors.forename: Jo
authors.initials: J
authors.lastname: Klaveness
authors.affiliation: Department of Neuropsychiatry and Psychosomatic Medicine, Oslo University Hospital, Oslo, Norway.
authors.forename: Ira
authors.initials: I
authors.lastname: Haraldsen
authors.affiliation: Department of Biomedical Engineering, University of California Davis, Davis, CA, USA; Department of Internal Medicine, Division of Hematology & Oncology, University of California Davis, 2921 Stockton Boulevard Sacramento, CA 95817, USA; Center for Molecular and Genomic Imaging, University of California Davis, Davis, CA, USA. Electronic address: jlsutcliffe@ucdavis.edu.
authors.forename: Julie L
authors.initials: JL
authors.lastname: Sutcliffe
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005462:Fluorine Radioisotopes / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D011966:Receptors, LHRH; D054852:Small Molecule Libraries
keywords: Fluorine-18; Gonadotropin-releasing hormone (GnRH) receptor antagonists; Luteinizing hormone releasing hormone (LHRH); Positron emission tomography (PET); Small molecule