title: In vivo assessment of [11C]MRB as a prospective PET ligand for imaging the norepinephrine transporter.
abstract: OBJECTIVE
  Antagonism of norepinephrine reuptake is now an important pharmacological strategy in the treatment of anxiety and depressive disorders, and many antidepressants have substantial potential occupancy of the norepinephrine transporter (NET) at recommended dosages. Despite the importance of understanding this transporter's role in psychiatric disease and treatment, a suitable radioligand for studying NET has been slow to emerge. (S,S)-Methylreboxetine (MRB) is among the more promising ligands recently adapted for positron emission tomography (PET), and the present study aimed to evaluate its potential for use in higher primates.
  
  
  METHODS
  Affinities for various brain targets were determined in vitro. PET studies were conducted in baboon under both test-retest and blocking conditions using 1 mg/kg nisoxetine.
  
  
  RESULTS
  MRB has sixfold higher affinity for NET than the serotonin transporter, and negligible affinity for other sites. PET studies in baboons showed little regional heterogeneity in binding and were minimally affected by pretreatment with the NET antagonist nisoxetine.
  
  
  CONCLUSIONS
  Despite improvement over previous ligands for imaging NET in vivo, the low signal to noise ratio indicates [(11)C]MRB lacks sensitivity and reliability as a PET radiotracer in humans.
authors.affiliation: Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, 1051 Riverside Drive, P.O. Box #42, New York, NY, 10032, USA.
authors.forename: Alin J
authors.initials: AJ
authors.lastname: Severance
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.|Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, 1051 Riverside Drive, P.O. Box #42, New York, NY, 10032, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Milak
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.|Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, 1051 Riverside Drive, P.O. Box #42, New York, NY, 10032, USA.
authors.forename: J S Dileep
authors.initials: JSD
authors.lastname: Kumar
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.
authors.forename: Jaya
authors.initials: J
authors.lastname: Prabhakaran
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.
authors.forename: Vattoly J
authors.initials: VJ
authors.lastname: Majo
authors.affiliation: Department of Radiology, Columbia University College of Physicians and Surgeons, New York, NY, USA.
authors.forename: Norman R
authors.initials: NR
authors.lastname: Simpson
authors.affiliation: Department of Radiology, Columbia University College of Physicians and Surgeons, New York, NY, USA.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Van Heertum
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.|Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, 1051 Riverside Drive, P.O. Box #42, New York, NY, 10032, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Arango
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.|Department of Radiology, Columbia University College of Physicians and Surgeons, New York, NY, USA.|Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, 1051 Riverside Drive, P.O. Box #42, New York, NY, 10032, USA.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA. rparsey@neuron.cpmc.columbia.edu.|Division of Brain Imaging, Department of Neuroscience, New York State Psychiatric Institute, 1051 Riverside Drive, P.O. Box #42, New York, NY, 10032, USA. rparsey@neuron.cpmc.columbia.edu.
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
mesh_terms: D018759:Adrenergic Uptake Inhibitors; D000818:Animals; D002250:Carbon Radioisotopes; D003952:Diagnostic Imaging / Q000295:instrumentation* / Q000379:methods; D005473:Fluoxetine / Q000031:analogs & derivatives; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008024:Ligands; D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D010215:Papio; D049268:Positron-Emission Tomography / Q000379:methods*; D000077593:Reboxetine; D012680:Sensitivity and Specificity; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D013997:Time Factors
chemical_list: D018759:Adrenergic Uptake Inhibitors; D002250:Carbon Radioisotopes; D008024:Ligands; D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D005473:Fluoxetine; C011386:nisoxetine; D000077593:Reboxetine