title: Test-retest reliability of (11)C-ORM-13070 in PET imaging of α2C-adrenoceptors in vivo in the human brain.
abstract: OBJECTIVE
  α2C-Adrenoceptors share inhibitory presynaptic functions with the more abundant α2A-adrenoceptor subtype, but they also have widespread postsynaptic modulatory functions in the brain. Research on the noradrenergic system of the human brain has been hampered by the lack of suitable PET tracers targeted to the α2-adrenoceptor subtypes.
  
  
  METHODS
  PET imaging with the specific α2C-adrenoceptor antagonist tracer [(11)C]ORM-13070 was performed twice in six healthy male subjects to investigate the test-retest reliability of tracer binding.
  
  
  RESULTS
  The bound/free ratio of tracer uptake relative to nonspecific uptake into the cerebellum during the time interval of 5 - 30 min was most prominent in the dorsal striatum: 0.77 in the putamen and 0.58 in the caudate nucleus. Absolute test-retest variability in bound/free ratios of tracer ranged from 4.3 % in the putamen to 29 % in the hippocampus. Variability was also <10 % in the caudate nucleus and thalamus. Intraclass correlation coefficients (ICC) ranged from 0.50 in the hippocampus to 0.89 in the thalamus (ICC >0.70 was also reached in the caudate nucleus, putamen, lateral frontal cortex and parietal cortex). The pattern of [(11)C]ORM-13070 binding, as determined by PET, was in good agreement with receptor density results previously derived from post-mortem autoradiography. PET data analysis results obtained with a compartmental model fit, the simplified reference tissue model and a graphical reference tissue analysis method were convergent with the tissue ratio method.
  
  
  CONCLUSIONS
  The results of this study support the use of [(11)C]ORM-13070 PET in the quantitative assessment of α2C-adrenoceptors in the human brain in vivo. Reliable assessment of specific tracer binding in the dorsal striatum is possible with the help of reference tissue ratios.
authors.affiliation: Clinical Research Services Turku CRST, University of Turku, Itäinen Pitkäkatu 4 B, 20520, Turku, Finland, juleht@utu.fi.
authors.forename: Jussi
authors.initials: J
authors.lastname: Lehto
authors.forename: Jere R
authors.initials: JR
authors.lastname: Virta
authors.forename: Vesa
authors.initials: V
authors.lastname: Oikonen
authors.forename: Anne
authors.initials: A
authors.lastname: Roivainen
authors.forename: Pauliina
authors.initials: P
authors.lastname: Luoto
authors.forename: Eveliina
authors.initials: E
authors.lastname: Arponen
authors.forename: Semi
authors.initials: S
authors.lastname: Helin
authors.forename: Johanna
authors.initials: J
authors.lastname: Hietamäki
authors.forename: Aila
authors.initials: A
authors.lastname: Holopainen
authors.forename: Marita
authors.initials: M
authors.lastname: Kailajärvi
authors.forename: Juha M
authors.initials: JM
authors.lastname: Peltonen
authors.forename: Juha
authors.initials: J
authors.lastname: Rouru
authors.forename: Jukka
authors.initials: J
authors.lastname: Sallinen
authors.forename: Kirsi
authors.initials: K
authors.lastname: Virtanen
authors.forename: Iina
authors.initials: I
authors.lastname: Volanen
authors.forename: Mika
authors.initials: M
authors.lastname: Scheinin
authors.forename: Juha O
authors.initials: JO
authors.lastname: Rinne
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging*; D004146:Dioxanes / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D010879:Piperazines / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D015203:Reproducibility of Results; D014018:Tissue Distribution
chemical_list: C000598340:1-(1-(2,3-dihydrobenzo(1,4)dioxin-2-yl)methyl)-4-(3-methoxymethylpyridin-2-yl)piperazine; D004146:Dioxanes; D010879:Piperazines; D019275:Radiopharmaceuticals; D018341:Receptors, Adrenergic, alpha-2