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 OX2 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]CH3I 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 34-36min 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.