We evaluated two 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 smallanimal 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.

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PET studies using [(11)C]XR9576 may be a promising approach for evaluating deficiency of the function of drug efflux transporters targeting intracranial diseases and tumors.

PET using [(11)C]GF120918 may be useful for evaluating the function of P-gp and BCRP. PET using P-gp/Bcrp knockout mice may be an effective method to understand the overall contributions the functions of P-gp and BCRP.

These results demonstrated the promising potential of [(11)C]gefitinib to serve as a PET ligand for in vivo imaging of NFSa-bearing mice.