title: Labeling and preliminary in vivo evaluation of the 5-HT(7) receptor selective agonist [(11)C]E-55888.
abstract: E-55888 has been identified as a selective serotonin 7 (5-HT7) receptor agonist. In this study, we describe the synthesis, radiolabeling and in vivo evaluation of [(11)C]E-55888 as a radioligand for positron emission tomography (PET) imaging. [(11)C]E-55888 was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60 °C giving isolated quantities in the range of 1.7-2.4 GBq. Studies in Danish Landrace pigs demonstrated that [(11)C]E-55888 has good brain uptake, however, the distribution in the brain tissue was dominated by non-specific binding, as binding could neither be displaced by the structurally different 5-HT7 receptor ligand SB-269970 nor by self-block with unlabeled E-55888. Based on these data, [(11)C]E-55888 does not show promise as a PET radioligand for imaging the 5-HT7 receptor in vivo.
authors: Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors: Hanne D
authors: HD
authors: Hansen
authors: Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
authors: Valdemar L
authors: VL
authors: Andersen
authors: PET and Cyclotron Unit, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors: Szabolcs
authors: S
authors: Lehel
authors: Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors: Janus H
authors: JH
authors: Magnussen
authors: Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors: Agnete
authors: A
authors: Dyssegaard
authors: Center for Molecular Medicine, Department of Neurology and Clinical Neuroscience, Karolinska Institute and Karolinska University Hospital, 17176 Stockholm, Sweden.
authors: Nikolas
authors: N
authors: Stroth
authors: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
authors: Jesper L
authors: JL
authors: Kristensen
authors: Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors: Gitte M
authors: GM
authors: Knudsen
authors: Center for Integrated Molecular Brain Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. Electronic address: matthias.herth@sund.ku.dk.
authors: Matthias M
authors: MM
authors: Herth
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013194:Staining and Labeling; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D002250:Carbon Radioisotopes; D011720:Pyrazoles; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C540144:dimethyl-(2-(3-(1,3,5-trimethyl-1H-pyrazol-4-yl)phenyl)ethyl)amine dihydrochloride; C104425:serotonin 7 receptor
keywords: 5-HT(7) receptor; Agonist; Carbon-11; E-55888; PET