title: Synthesis of fluorinated analogues of sphingosine-1-phosphate antagonists as potential radiotracers for molecular imaging using positron emission tomography.
abstract: Sphingosine-1-phosphate (S1P) receptors play major roles in cardiovascular, immunological and neurological diseases. The recent approval of the sphingolipid drug Fingolimod (Gilenya®), a sphingosine-1-phosphate agonist for relapsing multiple sclerosis, in 2010 exemplifies the potential for targeting sphingolipids for the treatment of human disorders. Moreover, non-invasive in vivo imaging of S1P receptors that are not available till now would contribute to the understanding of their role in specific pathologies and is therefore of preclinical interest. Based on fluorinated analogues of the S1P1 receptor antagonist W146 showing practically equal in vitro potency as the lead structure, the first S1P receptor antagonist [18F]-radiotracer has been synthesized and tested for in vivo imaging of the S1P1 receptor using positron emission tomography (PET). Though the tracer is serum stable, initial in vivo images show fast metabolism and subsequent accumulation of free [18F]fluoride in the bones.
authors.affiliation: Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, D-48149 Münster, Germany; NRW Graduate School of Chemistry, Westfälische Wilhelms-Universität Münster, Wilhelm-Klemm-Straße 10, D-48149 Münster, Germany.
authors.forename: Vysakh Pushpa
authors.initials: VP
authors.lastname: Prasad
authors.affiliation: Klinik für Nuklearmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude A1, D-48149 Münster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagner
authors.affiliation: Institute of Pathophysiology, University Hospital Essen, Hufelandstraße 55, D-45122 Essen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Keul
authors.affiliation: European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms-Universität Münster, Waldeyerstraße 15, D-48149 Münster, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hermann
authors.affiliation: Institute of Pathophysiology, University Hospital Essen, Hufelandstraße 55, D-45122 Essen, Germany.
authors.forename: Bodo
authors.initials: B
authors.lastname: Levkau
authors.affiliation: Klinik für Nuklearmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude A1, D-48149 Münster, Germany; European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms-Universität Münster, Waldeyerstraße 15, D-48149 Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), Westfälische Wilhelms-Universität Münster, Münster, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
authors.affiliation: Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, D-48149 Münster, Germany; European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms-Universität Münster, Waldeyerstraße 15, D-48149 Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), Westfälische Wilhelms-Universität Münster, Münster, Germany. Electronic address: haufe@uni-muenster.de.
authors.forename: Günter
authors.initials: G
authors.lastname: Haufe
mesh_terms: D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D005462:Fluorine Radioisotopes / Q000737:chemistry; D054879:Halogenation; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: C513113:3-amino-4-(3-hexylphenylamino)-4-oxobutylphosphonic acid; D000813:Anilides; D005462:Fluorine Radioisotopes; D063065:Organophosphonates; D019275:Radiopharmaceuticals; D049349:Receptors, Lysosphingolipid
keywords: Antagonist; Fluorination; Molecular imaging; Positron emission tomography (PET); Sphingosine-1-phosphate (S1P); [(18)F]-radiotracer