title: Synthesis and biological evaluation of positron emission tomography radiotracers targeting serotonin 4 receptors in brain: [18F]MNI-698 and [18F]MNI-699.
abstract: Two new benzodioxane derivatives were synthesized as candidates to image the serotonin 4 receptors by positron emission tomography (PET) and radiolabeled with fluorine-18 via a two-step procedure. Competition binding assays demonstrated that MNI-698 and MNI-699 had sub-nanomolar binding affinities against rat striatal 5-HT4 receptors (Ki of 0.20 and 0.07 nM, respectively). PET imaging in rhesus monkey showed that the regional brain distribution of [(18)F]MNI-698 and [(18)F]MNI-699 were consistent with the known densities of 5-HT4 in brain. [(18)F]MNI-698 and [(18)F]MNI-699 are among the first fluorine-18 radiotracers developed for imaging the 5-HT4 receptors in vivo and are currently under preclinical investigation in primates for future human use.
authors.affiliation: Molecular NeuroImaging LLC, New Haven, CT 06510, USA; Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA.
authors.forename: Fabien
authors.initials: F
authors.lastname: Caillé
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Morley
authors.forename: Adriana Alexandre S
authors.initials: AA
authors.lastname: Tavares
authors.forename: Caroline
authors.initials: C
authors.lastname: Papin
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Twardy
authors.forename: David
authors.initials: D
authors.lastname: Alagille
authors.forename: H Sharon
authors.initials: HS
authors.lastname: Lee
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: John P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: Olivier
authors.initials: O
authors.lastname: Barret
authors.forename: Gilles D
authors.initials: GD
authors.lastname: Tamagnan
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D004146:Dioxanes / Q000138:chemical synthesis* / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D008253:Macaca mulatta; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D044422:Receptors, Serotonin, 5-HT4 / Q000032:analysis* / Q000378:metabolism
chemical_list: C000593529:(1-(2-fluoroethyl)piperidin-4-yl)methyl 8-amino-7-chloro-2,3-dihydrobenzo(b)(1,4)dioxine-5-carboxylate; D004146:Dioxanes; D005462:Fluorine Radioisotopes; D010880:Piperidines; D019275:Radiopharmaceuticals; D044422:Receptors, Serotonin, 5-HT4
keywords: 5-HT(4); Alzheimer’s disease; Fluorine-18; PET imaging; Serotonin receptors