Imaging of I2 -imidazoline receptors by small-animal PET using 2-(3-fluoro-[4-11 C]tolyl)-4,5-dihydro-1 H -imidazole ([11 C]FTIMD)

Abstract Introduction Imidazoline receptors (IRs) have been established as distinct receptors, and have been categorized into at least two subtypes (I1 R and I2 R). I2 Rs are associated with depression, Alzheimer's disease, Huntington's disease and Parkinson's disease. A few positron emission tomography (PET) probes for I2 Rs have been synthesized, but a selective PET probe has not been evaluated for the imaging of I2 Rs by PET. We labeled a selective I2 R ligand 2-(3-fluoro-4-tolyl)-4,5-dihydro-1 H -imidazole (FTIMD) with11 C and performed the first imaging of I2 Rs by PET using 2-(3-fluoro-[4-11 C]tolyl)-4,5-dihydro-1 H -imidazole ([11 C]FTIMD). Methods [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. Results [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 I2 R. The radioactivity levels and VT values in the brain regions were prominently reduced by 1.0 mg/kg of BU224 pretreatment as compared with control. Conclusion [11 C]FTIMD showed specific binding to I2 Rs in rat brains with a high density of I2 R.