Synthesis and characterization of a potent, selective, radiolabeled substance-P antagonist for NK1 receptor quantitation: ([18F]SPA-RQ)

Mol Imaging Biol. 2004 Nov-Dec;6(6):373-84. doi: 10.1016/j.mibio.2004.08.001.


Purpose: To develop and characterize a radiolabelled Substance-P antagonist useful for quantitation of neurokinin-1 receptors in the brain via PET imaging.

Procedure: [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.

Conclusion: [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.

MeSH terms

  • Animals
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Fluorine Radioisotopes
  • Guinea Pigs
  • Humans
  • Hydrocarbons, Brominated / chemical synthesis
  • Hydrocarbons, Brominated / chemistry
  • Hydrocarbons, Brominated / metabolism
  • Hydrocarbons, Fluorinated / chemical synthesis
  • Hydrocarbons, Fluorinated / chemistry
  • Hydrocarbons, Fluorinated / metabolism
  • Macaca mulatta
  • Male
  • Molecular Structure
  • Positron-Emission Tomography
  • Receptors, Neurokinin-1 / analysis*
  • Receptors, Neurokinin-1 / metabolism
  • Sensitivity and Specificity
  • Spectrum Analysis
  • Substance P / antagonists & inhibitors*
  • Tissue Distribution


  • Fluorine Radioisotopes
  • Hydrocarbons, Brominated
  • Hydrocarbons, Fluorinated
  • Receptors, Neurokinin-1
  • bromofluoromethane
  • Substance P