title: (11)C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand.
abstract: Pimavanserin is a selective serotonin 2A receptor (5-HT2AR) inverse agonist that has shown promise for treatment of psychotic symptoms in patients with Parkinson's disease. Here, we detail the (11)C-labeling and subsequently evaluate pimavanserin as a PET-radioligand in pigs. [(11)C]Pimavanserin was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60°C giving radiochemical yields in the range of 1-1.7GBq (n=4). In Danish Landrace pigs the radio ligand readily entered the brain and displayed binding in the cortex in accordance with the distribution of 5-HT2ARs. However, this binding could not be blocked by either ketanserin or pimavanserin itself, indicating high nonspecific binding. The lack of displacement by the 5-HT2R antagonist and binding in the thalamus suggests that [(11)C]pimavanserin is not selective for the 5-HT2AR in pigs.
authors: Neurobiology Research Unit, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; Center for Integrated Molecular Brain Imaging, University of Copenhagen Rigshospitalet, 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: Neurobiology Research Unit, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; Center for Integrated Molecular Brain Imaging, University of Copenhagen Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors: Hanne D
authors: HD
authors: Hansen
authors: Neurobiology Research Unit, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; Center for Integrated Molecular Brain Imaging, University of Copenhagen Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors: Matthias M
authors: MM
authors: Herth
authors: Neurobiology Research Unit, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; Center for Integrated Molecular Brain Imaging, University of Copenhagen Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors: Agnete
authors: A
authors: Dyssegaard
authors: Neurobiology Research Unit, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; Center for Integrated Molecular Brain Imaging, University of Copenhagen Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors: Gitte M
authors: GM
authors: Knudsen
authors: Center for Integrated Molecular Brain Imaging, University of Copenhagen Rigshospitalet, 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: jesper.kristensen@sund.ku.dk.
authors: Jesper L
authors: JL
authors: Kristensen
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes / Q000032:analysis / Q000378:metabolism; D008024:Ligands; D008745:Methylation; D010880:Piperidines / Q000032:analysis / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000032:analysis / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000032:analysis / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000032:analysis / Q000378:metabolism*; D013552:Swine; D014508:Urea / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism
chemical_list: D002250:Carbon Radioisotopes; D008024:Ligands; D010880:Piperidines; D019275:Radiopharmaceuticals; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D014508:Urea; C510793:pimavanserin
keywords: 5-HT(2A) receptor; Carbon-11; N-methylation; PET; Pimavanserin