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

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-1H-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.

[(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.

[(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.

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.