title: PET study using [11C]FTIMD with ultra-high specific activity to evaluate I2-imidazoline receptors binding in rat brains.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555, Japan. kawamur@nirs.go.jp
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawamura
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Joji
authors.initials: J
authors.lastname: Yui
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Wakizaka
authors.forename: Tomoteru
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Akiko
authors.initials: A
authors.lastname: Hatori
authors.forename: Katsushi
authors.initials: K
authors.lastname: Kumata
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujinaga
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Masanao
authors.initials: M
authors.lastname: Ogawa
authors.forename: Nobuki
authors.initials: N
authors.lastname: Nengaki
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Fukumura
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D007093:Imidazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D054755:Imidazoline Receptors / Q000378:metabolism*; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: C552745:2-(3-fluorotolyl)-4,5-dihydro-1H-imidazole; D007093:Imidazoles; D054755:Imidazoline Receptors; C487767:imidazoline receptor 2