title: Synthesis and characterization of a potent, selective, radiolabeled substance-P antagonist for NK1 receptor quantitation: ([18F]SPA-RQ).
abstract: OBJECTIVE
  To develop and characterize a radiolabelled Substance-P antagonist useful for quantitation of neurokinin-1 receptors in the brain via PET imaging.
  
  
  METHODS
  [18F]SPA-RQ (Substance-P antagonist - receptor quantifier) was synthesized in good yield and high specific activity by alkylation of a BOC protected phenolate anion using [18F]bromofluoromethane. Removal of the BOC protecting group with trifluoroacetic acid gave [18F]SPA-RQ.
  
  
  RESULTS
  SPA-RQ has high affinity for human, rhesus monkey and guinea pig NK1 receptors (h-IC50=67 pM) and has a log P value of 1.8. Biodistribution studies in guinea pig showed that this tracer penetrates the blood-brain barrier and selectively labels NK1 receptors in the striatum and cortex.
  
  
  CONCLUSIONS
  [18F]SPA-RQ is a potent, high affinity Substance-P antagonist that can be conveniently labeled with high specific activity using [18F]fluoromethylbromide. This tracer is a useful tool for noninvasive imaging of central NK1 receptors.
authors.affiliation: Turku PET Centre, Turku, Finland.
authors.forename: Olof
authors.initials: O
authors.lastname: Solin
authors.forename: Olli
authors.initials: O
authors.lastname: Eskola
authors.forename: Terence G
authors.initials: TG
authors.lastname: Hamill
authors.forename: Jörgen
authors.initials: J
authors.lastname: Bergman
authors.forename: Pertti
authors.initials: P
authors.lastname: Lehikoinen
authors.forename: Tove
authors.initials: T
authors.lastname: Grönroos
authors.forename: Sarita
authors.initials: S
authors.lastname: Forsback
authors.forename: Merja
authors.initials: M
authors.lastname: Haaparanta
authors.forename: Tapio
authors.initials: T
authors.lastname: Viljanen
authors.forename: Christine
authors.initials: C
authors.lastname: Ryan
authors.forename: Raymond
authors.initials: R
authors.lastname: Gibson
authors.forename: Gerard
authors.initials: G
authors.lastname: Kieczykowski
authors.forename: Jarmo
authors.initials: J
authors.lastname: Hietala
authors.forename: Richard
authors.initials: R
authors.lastname: Hargreaves
authors.forename: H Donald
authors.initials: HD
authors.lastname: Burns
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D005462:Fluorine Radioisotopes; D006168:Guinea Pigs; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D018040:Receptors, Neurokinin-1 / Q000032:analysis* / Q000378:metabolism; D012680:Sensitivity and Specificity; D013057:Spectrum Analysis; D013373:Substance P / Q000037:antagonists & inhibitors*; D014018:Tissue Distribution
chemical_list: D005462:Fluorine Radioisotopes; D006842:Hydrocarbons, Brominated; D006845:Hydrocarbons, Fluorinated; D018040:Receptors, Neurokinin-1; C425968:bromofluoromethane; D013373:Substance P