title: [N-methyl-11C]Mirtazapine for positron emission tomography neuroimaging of antidepressant actions in humans.
abstract: BACKGROUND
  Many actions of antidepressant drugs cannot yet be studied using positron emission tomography (PET) neuroimaging due to lack of suitable radioligands. We believe that mirtazapine, radiolabeled with C-11, might be suitable for PET neuroimaging of alpha2-adrenoceptors in selected regions of the living human brain.
  
  
  OBJECTIVE
  To determine the regional central biodistribution and pharmacokinetics of [N-methyl-11C]mirtazapine in humans.
  
  
  METHODS
  Five healthy volunteers received an intravenous injection of [N-methyl-11C]mirtazapine for evaluating its metabolism, biodistribution and pharmacokinetics.
  
  
  RESULTS
  [N-methyl-11C]Mirtazapine entered the brain readily, with initial clearance from blood to tissue (K1) ranging from 0.31 ml/ml/min in amygdala to 0.54 ml/ml/min in thalamus. The rate of metabolism of [N-methyl-11C]mirtazapine in the bloodstream was relatively slow, with 20-40% of [11C]-derived radioactivity still present as parent compound at 60 min post-injection. The clearance of [N-methyl-11C]mirtazapine from the tissue compartment (k2') ranged from a low of 0.03 min(-1) in amygdala to a high of 0.06-0.07 min(-1) in thalamus and cerebellum. The volume of distribution (Ve') of [N-methyl-11C]mirtazapine was markedly greater in hippocampus and amygdala (11.3-12.0) than in cerebellum (6.7), with intermediate levels in the thalamus (9.4).
  
  
  CONCLUSIONS
  [N-methyl-11C]Mirtazapine has suitable properties for PET neuroimaging. We envision [N-methyl-11C]mirtazapine as a molecular probe for PET imaging of antidepressant actions at sites such as alpha2-adrenoceptors in the living human brain.
authors.affiliation: PET Center, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark.
authors.forename: Katalin
authors.initials: K
authors.lastname: Marthi
authors.forename: Steen
authors.initials: S
authors.lastname: Jakobsen
authors.forename: Dirk
authors.initials: D
authors.lastname: Bender
authors.forename: Søren B
authors.initials: SB
authors.lastname: Hansen
authors.forename: Stefan Bo
authors.initials: SB
authors.lastname: Smith
authors.forename: Flemming
authors.initials: F
authors.lastname: Hermansen
authors.forename: Raben
authors.initials: R
authors.lastname: Rosenberg
authors.forename: Donald F
authors.initials: DF
authors.lastname: Smith
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D006801:Humans; D008803:Mianserin / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D000078785:Mirtazapine; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D000316:Adrenergic alpha-Agonists; D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D000078785:Mirtazapine