title: Imaging of I2-imidazoline receptors by small-animal PET using 2-(3-fluoro-[4-11C]tolyl)-4,5-dihydro-1H-imidazole ([11C]FTIMD).
abstract: BACKGROUND
  Imidazoline receptors (IRs) have been established as distinct receptors, and have been categorized into at least two subtypes (I(1)R and I(2)R). I(2)Rs are associated with depression, Alzheimer's disease, Huntington's disease and Parkinson's disease. A few positron emission tomography (PET) probes for I(2)Rs have been synthesized, but a selective PET probe has not been evaluated for the imaging of I(2)Rs by PET. We labeled a selective I(2)R ligand 2-(3-fluoro-4-tolyl)-4,5-dihydro-1H-imidazole (FTIMD) with (11)C and performed the first imaging of I(2)Rs by PET using 2-(3-fluoro-[4-(11)C]tolyl)-4,5-dihydro-1H-imidazole ([(11)C]FTIMD).
  
  
  METHODS
  [(11)C]FTIMD was prepared by a palladium-promoted cross-coupling reaction of the tributylstannyl precursor and [(11)C]methyl iodide in the presence of tris(dibenzylideneacetone)dipalladium(0) and tri(o-tol)phosphine. Biodistribution was investigated in rats by tissue dissection. [(11)C]FTIMD metabolites were measured in brain tissues and plasma. Dynamic PET scans were acquired in rats, and the kinetic parameters estimated.
  
  
  RESULTS
  [(11)C]FTIMD was successfully synthesized with a suitable radioactivity for the injection. Co-injection with 0.1 mg/kg of cold FTIMD and BU224 induced a significant reduction in the brain-to-blood ratio 15 and 30 min after the injection. In metabolite analysis, unchanged [(11)C]FTIMD in the brain was high (98%) 30 min after the injection. In PET studies, high radioactivity levels were observed in regions with a high density of I(2)R. The radioactivity levels and V(T) values in the brain regions were prominently reduced by 1.0 mg/kg of BU224 pretreatment as compared with control.
  
  
  CONCLUSIONS
  [(11)C]FTIMD showed specific binding to I(2)Rs in rat brains with a high density of I(2)R.
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: Mika
authors.initials: M
authors.lastname: Naganawa
authors.forename: Fujiko
authors.initials: F
authors.lastname: Konno
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: Kazuhiko
authors.initials: K
authors.lastname: Yanamoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Hatori
authors.forename: Makoto
authors.initials: M
authors.lastname: Takei
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Kazuya
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Fukumura
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D007093:Imidazoles / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D054755:Imidazoline Receptors / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C552745:2-(3-fluorotolyl)-4,5-dihydro-1H-imidazole; D007093:Imidazoles; D054755:Imidazoline Receptors; C487767:imidazoline receptor 2