title: Mapping α2 adrenoceptors of the human brain with 11C-yohimbine.
abstract: A previous study from this laboratory suggested that (11)C-yohimbine, a selective α2-adrenoceptor antagonist, is an appropriate ligand for PET of α2 adrenoceptors that passes readily from blood to brain tissue in pigs but not in rodents. To test usefulness in humans, we determined blood-brain clearances, volumes of distribution, and receptor availability by means of PET with (11)C-yohimbine in healthy male adults.
  
  
  METHODS
  We recorded the distribution of (11)C-yohimbine with 90-min dynamic PET and sampled arterial blood to measure intact (11)C-yohimbine in plasma. For analysis, we coregistered PET images to individual MR images and automatically identified 27 volumes of interest. We used 1-tissue-compartment graphical analysis with 6 linearized solutions of the fundamental binding equation, with the metabolite-corrected arterial plasma curves as input function, to estimate the kinetic parameters of (11)C-yohimbine. With the lowest steady-state distribution volume (VT), determined in the corpus callosum, we calculated the binding potential (receptor availability) of the radioligand in other regions.
  
  
  RESULTS
  The linear regressions yielded similar estimates of the kinetic parameters. The cortical values of VT ranged from 0.82 mL cm(-3) in the right frontal cortex to 0.46 mL cm(-3) in the corpus callosum, with intermediate VT values in subcortical structures. Binding potentials averaged 0.6-0.8 in the cortex and 0.2-0.5 in subcortical regions.
  
  
  CONCLUSIONS
  The maps of (11)C-yohimbine binding to α2 adrenoceptors in human brain had the highest values in cortical areas and hippocampus, with moderate values in subcortical structures, as found also in vitro. The results confirm the usefulness of the tracer (11)C-yohimbine for mapping α2 adrenoceptors in human brain in vivo.
authors: Department of Nuclear Medicine and PET Centre, Aarhus University Hospitals, Aarhus, Denmark anah@ki.au.dk.
authors: Adjmal
authors: A
authors: Nahimi
authors: Department of Nuclear Medicine and PET Centre, Aarhus University Hospitals, Aarhus, Denmark.
authors: Steen
authors: S
authors: Jakobsen
authors: Department of Nuclear Medicine and PET Centre, Aarhus University Hospitals, Aarhus, Denmark.
authors: Ole L
authors: OL
authors: Munk
authors: Department of Nuclear Medicine and PET Centre, Aarhus University Hospitals, Aarhus, Denmark.
authors: Kim
authors: K
authors: Vang
authors: Department of Nuclear Medicine and PET Centre, Aarhus University Hospitals, Aarhus, Denmark.
authors: Jenny A
authors: JA
authors: Phan
authors: Department of Nuclear Medicine and PET Centre, Aarhus University Hospitals, Aarhus, Denmark.
authors: Anders
authors: A
authors: Rodell
authors: Department of Nuclear Medicine and PET Centre, Aarhus University Hospitals, Aarhus, Denmark Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland; and Department of Neurology, McGill University, Montreal, Quebec, Canada.
authors: Albert
authors: A
authors: Gjedde
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000000981:diagnostic imaging; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008024:Ligands; D008297:Male; D015233:Models, Statistical; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013997:Time Factors; D015016:Yohimbine
chemical_list: D002250:Carbon Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D019389:Cytochrome P-450 CYP2D6
keywords: 11C-yohimbine; brain; noradrenaline; positron emission tomography; α2 adrenoceptors