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

Introduction We recently developed a selective 11 C-labeled I 2 -imidazoline receptor (I 2 R) ligand, 2-(3-fluoro-4-[ 11 C]tolyl)-4,5-dihydro-1 H -imidazole ([ 11 C]FTIMD). [ 11 C]FTIMD showed specific binding to I 2 Rs in rat brains having a high density of I 2 R, as well as to I 2 Rs those in monkey brains, as illustrated by positron emission tomography (PET) and autoradiography. However, [ 11 C]FTIMD also showed moderate non-specific binding in rat brains. In order to increase the specificity for I 2 R in rat brains, we synthesized [ 11 C]FTIMD with ultra-high specific activity and evaluated its binding. Methods [ 11 C]FTIMD with ultra-high specific activity was prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [ 11 C]methyl iodide, which was produced by iodination of [ 11 C]methane using the single-pass method. Dynamic PET scans were conducted in rats, and the kinetic parameters were estimated. Results [ 11 C]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 I 2 R 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 [ 11 C]FTIMD with ultra-high specific activity were greater than those using [ 11 C]FTIMD with normal specific activity (17–34% decrease) in all brain regions investigated. Conclusion Quantitative PET using [ 11 C]FTIMD with ultra-high specific activity can contribute to the detection of small changes in I 2 R expression in the brain.