PURPOSE: 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). CONCLUSION: [(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.
PURPOSE: 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). CONCLUSION: [(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: J Logan; J S Fowler; N D Volkow; A P Wolf; S L Dewey; D J Schlyer; R R MacGregor; R Hitzemann; B Bendriem; S J Gatley Journal: J Cereb Blood Flow Metab Date: 1990-09 Impact factor: 6.200
Authors: Andrew C Emery; Sergey Pshenichkin; Guy Rodrigue Takoudjou; Ewa Grajkowska; Barry B Wolfe; Jarda T Wroblewski Journal: J Biol Chem Date: 2010-06-21 Impact factor: 5.157
Authors: Jinsoo Hong; Shuiyu Lu; Rong Xu; Jeih-San Liow; Alicia E Woock; Kimberly J Jenko; Robert L Gladding; Sami S Zoghbi; Robert B Innis; Victor W Pike Journal: Nucl Med Biol Date: 2015-07-23 Impact factor: 2.408
Authors: Rong Xu; Paolo Zanotti-Fregonara; Sami S Zoghbi; Robert L Gladding; Alicia E Woock; Robert B Innis; Victor W Pike Journal: J Med Chem Date: 2013-11-07 Impact factor: 7.446
Authors: Paolo Zanotti-Fregonara; Vanessa N Barth; Sami S Zoghbi; Jeih-San Liow; Eric Nisenbaum; Edward Siuda; Robert L Gladding; Denise Rallis-Frutos; Cheryl Morse; Johannes Tauscher; Victor W Pike; Robert B Innis Journal: EJNMMI Res Date: 2013-06-10 Impact factor: 3.138