Imidazoline receptors (IRs) have been established as distinct receptors, and have been categorized into at least two subtypes (I 1 R and I 2 R). I 2 Rs are associated with depression, Alzheimer's disease, Huntington's disease and Parkinson's disease. A few positron emission tomography (PET) probes for I 2 Rs have been synthesized, but a selective PET probe has not been evaluated for the imaging of I 2 Rs by PET. We labeled a selective I 2 R ligand 2-(3-fluoro-4-tolyl)-4,5-dihydro-1H-imidazole (FTIMD) with 11 C and performed the first imaging of I 2 Rs by PET using 2-(3-fluoro-[4- 11 C]tolyl)-4,5-dihydro-1H-imidazole ([ 11 C]FTIMD).[ 11 C]FTIMD was prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [ 11 C]methyl iodide in the presence of tris(dibenzylideneacetone)dipalladium(0) and tri(o-tol)phosphine. Biodistribution was investigated in rats by tissue dissection. [ 11 C]FTIMD metabolites were measured in brain tissues and plasma. Dynamic PET scans were acquired in rats, and the kinetic parameters estimated.[ 11 C]FTIMD was successfully synthesized with a suitable radioactivity for the injection. Co-injection with 0.1 mg/kg of cold FTIMD and BU224 induced a significant reduction in the brain-to-blood ratio 15 and 30 min after the injection. In metabolite analysis, unchanged [ 11 C]FTIMD in the brain was high (98%) 30 min after the injection. In PET studies, high radioactivity levels were observed in regions with a high density of I 2 R. The radioactivity levels and V T values in the brain regions were prominently reduced by 1.0 mg/kg of BU224 pretreatment as compared with control.[ 11 C]FTIMD showed specific binding to I 2 Rs in rat brains with a high density of I 2 R.