title: Serotonin 2A receptor agonist binding in the human brain with [(11)C]Cimbi-36: Test-retest reproducibility and head-to-head comparison with the antagonist [(18)F]altanserin.
abstract: BACKGROUND
  [(11)C]Cimbi-36 is a recently developed serotonin 2A (5-HT2A) receptor agonist positron emission tomography (PET) radioligand that has been successfully applied for human neuroimaging. Here, we investigate the test-retest variability of cerebral [(11)C]Cimbi-36 PET and compare [(11)C]Cimbi-36 and the 5-HT2A receptor antagonist [(18)F]altanserin.
  
  
  METHODS
  Sixteen healthy volunteers (mean age 23.9 ± 6.4years, 6 males) were scanned twice with a high resolution research tomography PET scanner. All subjects were scanned after a bolus of [(11)C]Cimbi-36; eight were scanned twice to determine test-retest variability in [(11)C]Cimbi-36 binding measures, and another eight were scanned after a bolus plus constant infusion with [(18)F]altanserin. Regional differences in the brain distribution of [(11)C]Cimbi-36 and [(18)F]altanserin were assessed with a correlation of regional binding measures and with voxel-based analysis.
  
  
  RESULTS
  Test-retest variability of [(11)C]Cimbi-36 non-displaceable binding potential (BPND) was consistently <5% in high-binding regions and lower for reference tissue models as compared to a 2-tissue compartment model. We found a highly significant correlation between regional BPNDs measured with [(11)C]Cimbi-36 and [(18)F]altanserin (mean Pearson's r: 0.95 ± 0.04) suggesting similar cortical binding of the radioligands. Relatively higher binding with [(11)C]Cimbi-36 as compared to [(18)F]altanserin was found in the choroid plexus and hippocampus in the human brain.
  
  
  CONCLUSIONS
  Excellent test-retest reproducibility highlights the potential of [(11)C]Cimbi-36 for PET imaging of 5-HT2A receptor agonist binding in vivo. Our data suggest that Cimbi-36 and altanserin both bind to 5-HT2A receptors, but in regions with high 5-HT2C receptor density, choroid plexus and hippocampus, the [(11)C]Cimbi-36 binding likely represents binding to both 5-HT2A and 5-HT2C receptors.
authors.affiliation: Neurobiology Research Unit, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Ettrup
authors.affiliation: Neurobiology Research Unit, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Svarer
authors.affiliation: Neurobiology Research Unit, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Brenda
authors.initials: B
authors.lastname: McMahon
authors.affiliation: Neurobiology Research Unit, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Sofi
authors.initials: S
authors.lastname: da Cunha-Bang
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Lehel
authors.affiliation: Department of Neuroanaesthesiology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Møller
authors.affiliation: Neurobiology Research Unit, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Agnete
authors.initials: A
authors.lastname: Dyssegaard
authors.affiliation: Neurobiology Research Unit, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Melanie
authors.initials: M
authors.lastname: Ganz
authors.affiliation: Neurobiology Research Unit, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Vincent
authors.initials: V
authors.lastname: Beliveau
authors.affiliation: Neurobiology Research Unit, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Louise Møller
authors.initials: LM
authors.lastname: Jørgensen
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Nic
authors.initials: N
authors.lastname: Gillings
authors.affiliation: Neurobiology Research Unit, Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: gmk@nru.dk.
authors.forename: Gitte Moos
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: D001596:Benzylamines / Q000378:metabolism / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D007650:Ketanserin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D059906:Neuroimaging / Q000379:methods; D010627:Phenethylamines / Q000378:metabolism / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000378:metabolism / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D058826:Serotonin 5-HT2 Receptor Agonists / Q000378:metabolism / Q000493:pharmacokinetics*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000378:metabolism / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D001596:Benzylamines; D002250:Carbon Radioisotopes; C586246:Cimbi-36; D005462:Fluorine Radioisotopes; D010627:Phenethylamines; D019275:Radiopharmaceuticals; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; C071983:altanserin; D007650:Ketanserin
keywords: 5-HT; Agonist; Neuroimaging; Positron emission tomography; Radiotracer evaluation; Test–retest variability