title: Visualization and quantification of neurokinin-1 (NK1) receptors in the human brain.
abstract: OBJECTIVE
  This study was conducted to develop a new positron emission tomography (PET) method to visualize neurokinin-1 (NK(1)) receptor systems in the human brain in vivo in order to examine their neuroanatomical distribution and facilitate investigations of the role of substance P, NK(1) receptors, and NK(1) receptor antagonists in central nervous system (CNS) function and dysfunction.
  
  
  METHODS
  PET studies were conducted in 10 healthy male volunteers using a novel selective, high-affinity NK(1) receptor antagonist labeled with fluorine-18 to very high specific radioactivity (up to 2000 GBq/micromol) [F-18]SPA-RQ. Data were collected in 3D mode for greatest sensitivity. Different modeling methods were compared and regional receptor distributions determined for comparison with in vitro autoradiographic studies using postmortem human brain slices with [F-18]SPA-RQ.
  
  
  RESULTS
  The studies showed that the highest uptake of [F-18]SPA-RQ was observed in the caudate and putamen. Lower binding was found in globus pallidus and substantia nigra. [F-18]SPA-RQ uptake was also widespread throughout the neocortex and limbic cortex including amygdala and hippocampus. There was very low specific uptake of the tracer in the cerebellar cortex. The distribution pattern was confirmed using in vitro receptor autoradiography with [F-18]SPA-RQ on postmortem human brain slices. Kinetic modeling of the [F-18]SPA-RQ uptake data indicated a binding potential between 4 and 5 in the basal ganglia and between 1.5 and 2.5 in the cortical regions.
  
  
  CONCLUSIONS
  [F-18]SPA-RQ is a novel tool for exploration of the functions of NK(1) receptors in man. [F-18]SPA-RQ can be used to define receptor pharmacodynamics and focus dose selection of novel NK(1) receptor antagonists in clinical trials thereby ensuring adequate proof of concept testing particularly in therapeutic applications related to CNS dysfunction.
authors.affiliation: Neuropsychiatric Imaging, Turku PET Centre, Turku University Central Hospital, Finland.
authors.forename: Jarmo
authors.initials: J
authors.lastname: Hietala
authors.forename: Mikko J
authors.initials: MJ
authors.lastname: Nyman
authors.forename: Olli
authors.initials: O
authors.lastname: Eskola
authors.forename: Aki
authors.initials: A
authors.lastname: Laakso
authors.forename: Tove
authors.initials: T
authors.lastname: Grönroos
authors.forename: Vesa
authors.initials: V
authors.lastname: Oikonen
authors.forename: Jörgen
authors.initials: J
authors.lastname: Bergman
authors.forename: Merja
authors.initials: M
authors.lastname: Haaparanta
authors.forename: Sarita
authors.initials: S
authors.lastname: Forsback
authors.forename: Päivi
authors.initials: P
authors.lastname: Marjamäki
authors.forename: Pertti
authors.initials: P
authors.lastname: Lehikoinen
authors.forename: Michael
authors.initials: M
authors.lastname: Goldberg
authors.forename: Donald
authors.initials: D
authors.lastname: Burns
authors.forename: Terence
authors.initials: T
authors.lastname: Hamill
authors.forename: Wai-Si
authors.initials: WS
authors.lastname: Eng
authors.forename: Alexandre
authors.initials: A
authors.lastname: Coimbra
authors.forename: Richard
authors.initials: R
authors.lastname: Hargreaves
authors.forename: Olof
authors.initials: O
authors.lastname: Solin
mesh_terms: D000328:Adult; D001158:Arteries / Q000378:metabolism; D001345:Autoradiography; D001479:Basal Ganglia / Q000378:metabolism; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D007700:Kinetics; D008297:Male; D008636:Mesencephalon / Q000033:anatomy & histology / Q000378:metabolism; D008954:Models, Biological; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1 / Q000032:analysis* / Q000378:metabolism*; D012015:Reference Standards; D012886:Skull / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1