title: Synthesis and evaluation of PET probes for the imaging of I2 imidazoline receptors in peripheral tissues.
abstract: BACKGROUND
  To explore the possible use of positron emission tomography (PET) probes for imaging of I(2)-imidazoline receptors (I(2)Rs) in peripheral tissues, we labeled two new I(2)R ligands, 2-[2-(o-tolyl)vinyl]-4,5-dihydro-1H-imidazole (K(i) for I(2)Rs, 3.7 nM) and 2-[2-(o-tolyl)ethyl]-4,5-dihydro-1H-imidazole (K(i) for I(2)Rs, 1.7 nM) with (11)C ([(11)C]metrazoline and [(11)C]TEIMD), respectively, and evaluated these ligands and the recently developed I(2)R ligand 2-[3-fluoro-[4-(11)C]tolyl]-4,5-dihydro-1H-imidazole ([(11)C]FTIMD) by in vivo studies.
  
  
  METHODS
  [(11)C]Metrazoline and [(11)C]TEIMD were prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [(11)C]methyl iodide. Their biodistribution in mice was investigated by tissue dissection. In addition, PET scans and metabolite analysis were performed.
  
  
  RESULTS
  [(11)C]Metrazoline and [(11)C]TEIMD were successfully synthesized with a suitable radioactivity for injection. In the liver and pancreas expressing I(2)Rs, coinjection with the high-affinity I(2)R ligand, BU224, induced a reduction in the radioactivity level at 30 min after injection of [(11)C]metrazoline and [(11)C]FTIMD. However, the radioactivity level after injection of [(11)C]TEIMD was unchanged. In the PET study, coinjection with BU224 induced a decrease in the radioactivity level in the liver and pancreas after more than 15 min of injection of [(11)C]metrazoline and [(11)C]FTIMD as compared with the results obtained for controls. In metabolite analysis, coinjection with BU224 induced a significant reduction in the percentage of unchanged [(11)C]metrazoline at 30 min after injection as compared with that in the control, although no significant difference was observed in the percentage of unchanged [(11)C]FTIMD.
  
  
  CONCLUSIONS
  [(11)C]Metrazoline may be a more useful PET probe than [(11)C]FTIMD for imaging of I(2)Rs in peripheral tissues.
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: Joji
authors.initials: J
authors.lastname: Yui
authors.forename: Fujiko
authors.initials: F
authors.lastname: Konno
authors.forename: Tomoteru
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Akiko
authors.initials: A
authors.lastname: Hatori
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Wakizaka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujinaga
authors.forename: Katushi
authors.initials: K
authors.lastname: Kumata
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: Kazuhiko
authors.initials: K
authors.lastname: Yanamoto
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Fukumura
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D006847:Hydrocarbons, Iodinated / Q000493:pharmacokinetics*; D007093:Imidazoles / Q000493:pharmacokinetics*; D054755:Imidazoline Receptors / Q000378:metabolism*; D008024:Ligands; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D051379:Mice; D010179:Pancreas / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D014018:Tissue Distribution
chemical_list: C105826:BU 224; D002250:Carbon Radioisotopes; D006847:Hydrocarbons, Iodinated; D007093:Imidazoles; D054755:Imidazoline Receptors; D008024:Ligands; C487767:imidazoline receptor 2; C014055:methyl iodide