title: Synthesis and evaluation of fluorinated fingolimod (FTY720) analogues for sphingosine-1-phosphate receptor molecular imaging by positron emission tomography.
abstract: Sphingosine-1-phosphate (S1P) is a lysophospholipid that evokes a variety of biological responses via stimulation of a set of cognate G-protein coupled receptors (GPCRs): S1P1-S1P5. S1P and its receptors (S1PRs) play important roles in the immune, cardiovascular, and central nervous systems and have also been implicated in carcinogenesis. Recently, the S1P analogue Fingolimod (FTY720) has been approved for the treatment of patients with relapsing multiple sclerosis. This work presents the synthesis of various fluorinated structural analogues of FTY720, their in vitro and in vivo biological testing, and their development and application as [(18)F]radiotracers for the study of S1PR biodistribution and imaging in mice using small-animal positron emission tomography (PET).
authors.affiliation: †Organisch-Chemisches Institut and International NRW Graduate School of Chemistry, 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: Rizwan S
authors.initials: RS
authors.lastname: Shaikh
authors.affiliation: †Organisch-Chemisches Institut and International NRW Graduate School of Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, D-48149 Münster, Germany.
authors.forename: Stefanie S
authors.initials: SS
authors.lastname: Schilson
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.forename: Sven
authors.initials: S
authors.lastname: Hermann
authors.affiliation: #Institute of Pathophysiology, Westdeutsches Herz- und Gefäßzentrum, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, D-45122 Essen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Keul
authors.affiliation: #Institute of Pathophysiology, Westdeutsches Herz- und Gefäßzentrum, University Hospital Essen, University of Duisburg-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.
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
authors.affiliation: †Organisch-Chemisches Institut and International NRW Graduate School of Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, D-48149 Münster, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Haufe
mesh_terms: D000818:Animals; D000068876:Fingolimod Hydrochloride; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D054879:Halogenation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*; D011409:Propylene Glycols / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D049349:Receptors, Lysosphingolipid / Q000032:analysis*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D000081025:Sphingosine-1-Phosphate Receptors
chemical_list: D005462:Fluorine Radioisotopes; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; C556330:S1pr1 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine