title: Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [18F]FITM.
abstract: OBJECTIVE
  In this study, we evaluate the utility of 4-[(18)F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([(18)F]FITM) as a positron emission tomography (PET) ligand for imaging of the metabotropic glutamate receptor subtype 1 (mGluR1) in rat and monkey brains.
  
  
  METHODS
  In vivo distribution of [(18)F]FITM in brains was evaluated by PET scans with or without the mGluR1-selective antagonist (JNJ16259685). Kinetic parameters of monkey PET data were obtained using the two-tissue compartment model with arterial blood sampling.
  
  
  RESULTS
  In PET studies in rat and monkey brains, the highest uptake of radioactivity was in the cerebellum, followed by moderate uptake in the thalamus, hippocampus and striatum. The lowest uptake of radioactivity was detected in the pons. These uptakes in all brain regions were dramatically decreased by pre-administration of JNJ16259685. In kinetic analysis of monkey PET, the highest volume of distribution (V(T)) was detected in the cerebellum (V(T) = 11.5).
  
  
  CONCLUSIONS
  [(18)F]FITM has an excellent profile as a PET ligand for mGluR1 imaging. PET with [(18)F]FITM may prove useful for determining the regional distribution and density of mGluR1 and the mGluR1 occupancy of drugs in human brains.
authors: Molecular Imaging Centre, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.
authors: Tomoteru
authors: T
authors: Yamasaki
authors: Masayuki
authors: M
authors: Fujinaga
authors: Jun
authors: J
authors: Maeda
authors: Kazunori
authors: K
authors: Kawamura
authors: Joji
authors: J
authors: Yui
authors: Akiko
authors: A
authors: Hatori
authors: Yuichiro
authors: Y
authors: Yoshida
authors: Yuji
authors: Y
authors: Nagai
authors: Masaki
authors: M
authors: Tokunaga
authors: Makoto
authors: M
authors: Higuchi
authors: Tetsuya
authors: T
authors: Suhara
authors: Toshimitsu
authors: T
authors: Fukumura
authors: Ming-Rong
authors: MR
authors: Zhang
mesh_terms: D000818:Animals; D001345:Autoradiography; D001549:Benzamides / Q000493:pharmacokinetics; D001921:Brain / Q000166:cytology / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005240:Feasibility Studies; D000882:Haplorhini; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013844:Thiazoles / Q000493:pharmacokinetics
chemical_list: C560416:4-fluoro-N-(4-(6-(isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl)-N-methylbenzamide; D001549:Benzamides; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles; C104077:metabotropic glutamate receptor type 1