Characterization of 1-(2-[18F] fluoro-3-pyridyl)-4-(2-isopropyl-1-oxo- isoindoline-5-yl)-5-methyl-1H-1,2,3-triazole, a PET ligand for imaging the metabotropic glutamate receptor type 1 in rat and monkey brains.

We developed 1-(2-[(18) F]fluoro-3-pyridyl)-4-(2-isopropyl-1-oxo-isoindoline-5-yl)-5-methyl-1H-1,2,3-triazole ([(18) F]FPIT) as a promising positron emission tomography (PET) ligand for in vitro and in vivo imaging of metabotropic glutamate receptor type 1 (mGluR1) in rat and monkey brains. In vitro autoradiography with [(18) F]FPIT was used to determine the distribution of radioactivity in rat and monkey brains. In vivo experiments were performed using dissection and small-animal PET on rats, and PET on monkey. Metabolite analysis was performed on rat plasma and brain, and monkey plasma. Autoradiography of rat and monkey brains showed that [(18) F]FPIT binding is aligned with the reported distribution of mGluR1 with high specific binding in the cerebellum and thalamus. PET study on rat and monkey showed high brain uptake and distribution patterns consistent with those seen in the autoradiographic studies. The radioactivity in the brain was significantly decreased by pre-treatment with unlabeled FPIT, indicative of a specific signal for mGluR1 that was inhibited by mGluR1-selective ligand JNJ-16259865 in the brain. Metabolite analysis showed that the percentage of unchanged [(18) F]FPIT was 89% in the brain homogenate of rat at 90 min after injection. In the monkey plasma, the percentage of unchanged form was 50% at 90 min. [(18) F]FPIT produced in vitro and in vivo signals to visualize mGluR1 expression in rat and monkey brains, suggesting the usefulness of [(18) F]FPIT for imaging mGluR1 in human brain.