The functions of I 2 -imidazoline receptors (I 2 Rs) are unknown, but evidence exists for their involvement in various neuropsychiatric disorders. Although a few positron emission tomography (PET) I 2 R ligands have been developed, of which [ 11 C]FTIMD and [ 11 C]BU99008 were evaluated as PET I 2 R imaging ligands in monkeys, no human PET imaging study using an I 2 R-selective PET ligand has been conducted yet. Thus, we synthesized an 18 F-labeled I 2 R-selective ligand (BU99018 or FEBU, Ki for I 2 Rs=2.6nM), and evaluated its application using rodents in PET imaging in vivo toward the development of a clinically-useful I 2 R PET imaging ligand.[ 18 F]FEBU was synthesized by the reaction of its precursor and [ 18 F]fluoroethyl bromide. A biodistribution and brain PET study were conducted in mice and rats respectively.[ 18 F]FEBU was successfully synthesized yielding a radioactivity suitable for injection (10.1±5.3% at the end of the irradiation (n=10) based on 18 F − ). The specific activity at end of synthesis (EOS) was 40–147TBq/mmol (n=10). The radiochemical purity was >99% at EOS and remained >99% for 90min after EOS. In mice brain uptake was relatively high. In the blocking study with the co-injection of the high-affinity I 2 R ligand BU224 (1mg/kg b.w.) brain uptake was significantly decreased 30min post-injection. In the PET studies the radioactivity was highly accumulated in the I 2 R-rich hypothalamus. Pretreatment with BU224 (1mg/kg b.w.) significantly decreased the radioactivity in the hypothalamus to 23% of that of the control from 60 to 90min post-injection.[ 18 F]FEBU was sufficiently stable as a PET ligand and had a relatively high specific binding affinity for I 2 Rs in rats and mice.