Radiosynthesis and evaluation of [11C]EMPA as a potential PET tracer for orexin 2 receptors

Changning Wang, Christian K. Moseley, Stephen M. Carlin, Colin M. Wilson, Ramesh Neelamegam, Jacob M. Hooker

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


EMPA is a selective antagonist of orexin 2 (OX2) receptors. Previous literature with [3H]-EMPA suggest that it may be used as an imaging agent for OX2 receptors; however, brain penetration is known to be modest. To evaluate the potential of EMPA as a PET radiotracer in non-human primate (as a step to imaging in man), we radiolabeled EMPA with carbon-11. Radiosynthesis of [11C]N-ethyl-2-(N-(6-methoxypyridin-3- yl)-2-methylphenylsulfonamido)-N-(pyridin-3-ylmethyl)acetamide ([ 11C]EMPA), and evaluation as a potential PET tracer for OX 2 receptors is described. Synthesis of an appropriate non-radioactive O-desmethyl precursor was achieved from EMPA with sodium iodide and chlorotrimethylsilane. Selective O-methylation using [11C]CH 3I in the presence of cesium carbonate in DMSO at room temp afforded [11C]EMPA in 1.5-2.5% yield (non-decay corrected relative to trapped [11C]CH3I at EOS) with ≥95% chemical and radiochemical purities. The total synthesis time was 34-36 min from EOB. Studies in rodent suggested that uptake in tissue was dominated by nonspecific binding. However, [11C]EMPA also showed poor uptake in both rats and baboon as measured with PET imaging.

Original languageEnglish (US)
Pages (from-to)3389-3392
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Issue number11
StatePublished - Jun 1 2013
Externally publishedYes


  • Brain
  • Carbon-11
  • EMPA
  • Orexin
  • PET radiotracer

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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