PET study using [11C]FTIMD with ultra-high specific activity to evaluate I2-imidazoline receptors binding in rat brains

IntroductionWe recently developed a selective 11C-labeled I2-imidazoline receptor (I2R) ligand, 2-(3-fluoro-4-[11C]tolyl)-4,5-dihydro-1H-imidazole ([11C]FTIMD). [11C]FTIMD showed specific binding to I2Rs in rat brains having a high density of I2R, as well as to I2Rs those in monkey brains, as illustrated by positron emission tomography (PET) and autoradiography. However, [11C]FTIMD also showed moderate non-specific binding in rat brains. In order to increase the specificity for I2R in rat brains, we synthesized [11C]FTIMD with ultra-high specific activity and evaluated its binding.Methods[11C]FTIMD with ultra-high specific activity was prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [11C]methyl iodide, which was produced by iodination of [11C]methane using the single-pass method. Dynamic PET scans were conducted in rats, and the kinetic parameters were estimated.Results[11C]FTIMD with ultra-high specific activity was successfully synthesized with an appropriate level of radioactivity and ultra-high specific activity (4470±1660 GBq/μmol at end of synthesis, n=11) for injection. In the PET study, distribution volume (VT) values in all the brain regions investigated whether I2R expression was greatly reduced in BU224-pretreatead rats compared with control rats (29–45% decrease). Differences in VT values between control and BU224-pretreated rats using [11C]FTIMD with ultra-high specific activity were greater than those using [11C]FTIMD with normal specific activity (17–34% decrease) in all brain regions investigated.ConclusionQuantitative PET using [11C]FTIMD with ultra-high specific activity can contribute to the detection of small changes in I2R expression in the brain.