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

Abstract Introduction We recently developed a selective11 C-labeled I2 -imidazoline receptor (I2 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 I2 Rs in rat brains having a high density of I2 R, as well as to I2 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 I2 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 ( VT ) values in all the brain regions investigated whether I2 R 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 [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 I2 R expression in the brain.