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 C-11-labeled I-2-imidazoline receptor (I2R) ligand, 2-(3-fluoro-4[C-11]tolyl)-4,5-dihydro-1H-imidazole ([C-11]FTIMD). [C-11]FTIMD showed specific binding to I(2)Rs in rat brains having a high density of I2R, as well as to I(2)Rs those in monkey brains, as illustrated by positron emission tomography (PET) and autoradiography. However, [C-11]FTIMD also showed moderate non-specific binding in rat brains. In order to increase the specificity for 1,2 in rat brains, we synthesized [C-11]FTIMD with ultra-high specific activity and evaluated its binding. Methods: [C-11)FTIMD with ultra-high specific activity was prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [C-11]methyl iodide, which was produced by iodination of [C-11]methane using the single-pass method. Dynamic PET scans were conducted in rats, and the kinetic parameters were estimated. Results: [C-11]FTIMD with ultra-high specific activity was successfully synthesized with an appropriate level of radioactivity and ultra-high specific activity (4470 +/- 1660 GBq/mu mol 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 [C-11]FTIMD with ultra-high specific activity were greater than those using [C-11]FTIMD with normal specific activity (17-34% decrease) in all brain regions investigated. Conclusion: Quantitative PET using [C-11]FTIMD with ultra-high specific activity can contribute to the detection of small changes in I2R expression in the brain. (C) 2012 Elsevier Inc. All rights reserved.