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.Methods¹¹C]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.Results¹¹C]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 (V_T) 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 V_T 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.