title: Quantification of the neurokinin 1 receptor ligand [¹¹C]R116301.
abstract: OBJECTIVE
  Neurokinin 1 (NK1) receptors have been implicated in depression, anxiety, and pain perception. Recently, it was shown that, in the human brain, a specific NK1 receptor-related signal was obtained with the novel radioligand, [¹¹C]R116301, using positron emission tomography. The purpose of this study was to evaluate various methods for quantifying specific [¹¹C]R116301 binding.
  
  
  METHODS
  Two dynamic 90-min [¹¹C]R116301 scans, separated by 5 h, were performed in 11 healthy volunteers. In three patients, the second scan was performed after an oral blocking dose of 125 mg of aprepitant, whereas in the other eight, no intervention was performed (test-retest). Whole striatum was used as the tissue of interest, as it has the highest density of NK1 receptors. Cerebellum was used as the reference tissue.
  
  
  RESULTS
  Reference tissue models were stable with the simplified reference tissue model (SRTM) performing best. Average (± standard deviation) SRTM-derived mean nondisplaceable binding potential (BP(ND)) of all (first) baseline scans was 0.64±0.31 (n=11), which reduced to -0.01±0.03 (n=3) after aprepitant administration. Test-retest results showed low variability (14.0±10.7%) and excellent reliability, as indicated by the intraclass correlation coefficient (0.93). The ratio of standardized uptake values of striatum and cerebellum minus 1, an approximation of BP(ND), showed very low variability (6.2±3.1%) with excellent reliability (intraclass correlation coefficient=0.98), and correlated well with SRTM-derived BP(ND) (R²=0.96).
  
  
  CONCLUSIONS
  SRTM is the model of choice for quantifying [¹¹C]R116301 binding. Semiquantitative tissue ratios hold promise for routine clinical applications.
authors.affiliation: Department of Nuclear Medicine, Psychiatry, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Saskia P
authors.initials: SP
authors.lastname: Wolfensberger
authors.forename: Kaoru
authors.initials: K
authors.lastname: Maruyama
authors.forename: Bart N
authors.initials: BN
authors.lastname: van Berckel
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.forename: Anu J
authors.initials: AJ
authors.lastname: Airaksinen
authors.forename: Ronald
authors.initials: R
authors.lastname: Boellaard
authors.forename: Gert
authors.initials: G
authors.lastname: Luurtsema
authors.forename: Wieb
authors.initials: W
authors.lastname: Reddingius
authors.forename: Frans E
authors.initials: FE
authors.lastname: Janssens
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
authors.forename: Josée E
authors.initials: JE
authors.lastname: Leysen
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
mesh_terms: D000328:Adult; D000440:Butanols / Q000097:blood / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008293:Malates; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism; D010880:Piperidines; D049268:Positron-Emission Tomography; D011485:Protein Binding; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D012015:Reference Standards; D013379:Substrate Specificity; D055815:Young Adult
chemical_list: D000440:Butanols; D002250:Carbon Radioisotopes; D008024:Ligands; D008293:Malates; D010880:Piperidines; C400708:R116301; D018040:Receptors, Neurokinin-1