UNLABELLED: We evaluated two (18)F-labeled PET ligands, N-benzyl-N-ethyl-2-[7,8-dihydro-7-(2-(18)F-fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide ((18)F-FEAC) and N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-(18)F-fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide ((18)F-FEDAC), by investigating their kinetics in the monkey brain and by performing in vitro and in vivo imaging of translocator protein (18 kDa) (TSPO) in the infarcted rat brain. METHODS: Dissection was used to determine the distribution of (18)F-FEAC and (18)F-FEDAC in mice, whereas PET was used for a monkey. With each (18)F-ligand, in vitro autoradiography and small-animal PET were performed on infarcted rat brains. RESULTS: (18)F-FEAC and (18)F-FEDAC had a high uptake of radioactivity in the heart, lung, and other TSPO-rich organs of mice. In vitro autoradiography showed that the binding of each (18)F-ligand significantly increased on the ipsilateral side of rat brains, compared with the contralateral side. In a small-animal PET study, PET summation images showed the contrast of radioactivity between ipsilateral and contralateral sides. Pretreatment with TSPO ligands N-benzyl-N-ethyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide (AC-5216) or (R)-N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide (PK11195) diminished the difference in uptake between the 2 sides. The PET study showed that each (18)F-ligand had uptake and distribution patterns in the monkey brain similar to those of (11)C-AC-5216. After injection into the monkey during PET, the uptake of each (18)F-ligand in the brain decreased over time whereas (11)C-AC-5216 did not. In the brain homogenate of mice, the percentage of the fraction corresponding to intact (18)F-FEAC and (18)F-FEDAC was 68% and 75% at 30 min after injection. In monkey plasma, each (18)F-ligand was scarcely metabolized until the end of the PET scan. CONCLUSION: (18)F-FEAC and (18)F-FEDAC produced in vitro and in vivo signals allowing visualization of the increase in TSPO expression in the infarcted rat brain. The kinetics of both (18)F-ligands in the monkey brain and tolerance for in vivo metabolism suggested their usefulness for imaging studies of TSPO in primates.
UNLABELLED: We evaluated two (18)F-labeled PET ligands, N-benzyl-N-ethyl-2-[7,8-dihydro-7-(2-(18)F-fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide ((18)F-FEAC) and N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-(18)F-fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide ((18)F-FEDAC), by investigating their kinetics in the monkey brain and by performing in vitro and in vivo imaging of translocator protein (18 kDa) (TSPO) in the infarctedrat brain. METHODS: Dissection was used to determine the distribution of (18)F-FEAC and (18)F-FEDAC in mice, whereas PET was used for a monkey. With each (18)F-ligand, in vitro autoradiography and small-animal PET were performed on infarctedrat brains. RESULTS: (18)F-FEAC and (18)F-FEDAC had a high uptake of radioactivity in the heart, lung, and other TSPO-rich organs of mice. In vitro autoradiography showed that the binding of each (18)F-ligand significantly increased on the ipsilateral side of rat brains, compared with the contralateral side. In a small-animal PET study, PET summation images showed the contrast of radioactivity between ipsilateral and contralateral sides. Pretreatment with TSPO ligands N-benzyl-N-ethyl-2-(7-methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl)acetamide (AC-5216) or (R)-N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide (PK11195) diminished the difference in uptake between the 2 sides. The PET study showed that each (18)F-ligand had uptake and distribution patterns in the monkey brain similar to those of (11)C-AC-5216. After injection into the monkey during PET, the uptake of each (18)F-ligand in the brain decreased over time whereas (11)C-AC-5216 did not. In the brain homogenate of mice, the percentage of the fraction corresponding to intact (18)F-FEAC and (18)F-FEDAC was 68% and 75% at 30 min after injection. In monkey plasma, each (18)F-ligand was scarcely metabolized until the end of the PET scan. CONCLUSION: (18)F-FEAC and (18)F-FEDAC produced in vitro and in vivo signals allowing visualization of the increase in TSPO expression in the infarctedrat brain. The kinetics of both (18)F-ligands in the monkey brain and tolerance for in vivo metabolism suggested their usefulness for imaging studies of TSPO in primates.
Authors: Frederick M Lartey; G-One Ahn; Bin Shen; Keith-Travis Cord; Tenille Smith; Joshua Y Chua; Sahar Rosenblum; Hongguang Liu; Michelle L James; Sophia Chernikova; Star W Lee; Laura J Pisani; Rabindra Tirouvanziam; John W Chen; Theo D Palmer; Frederick T Chin; Raphael Guzman; Edward E Graves; Billy W Loo Journal: Mol Imaging Biol Date: 2013-07-09 Impact factor: 3.488
Authors: Frederick M Lartey; G-One Ahn; Rehan Ali; Sahar Rosenblum; Zheng Miao; Natasha Arksey; Bin Shen; Marta Vilalta Colomer; Marjan Rafat; Hongguang Liu; Miguel A Alejandre-Alcazar; John W Chen; Theo Palmer; Frederick T Chin; Raphael Guzman; Billy W Loo; Edward Graves Journal: Mol Imaging Biol Date: 2014-12 Impact factor: 3.488
Authors: S Eberl; A Katsifis; M A Peyronneau; L Wen; D Henderson; C Loc'h; I Greguric; J Verschuer; T Pham; P Lam; F Mattner; A Mohamed; M J Fulham Journal: Eur J Nucl Med Mol Imaging Date: 2016-10-04 Impact factor: 9.236