We designed four novel acetamidobenzoxazolone compounds 7a-d as candidates for positron emission tomography (PET) radiotracers for imaging the translocator protein (18 kDa, TSPO) in ischemic brain and glioma. Among these compounds, 2-(5-(6-fluoropyridin-3-yl)-2-oxobenzo[d]oxazol-3(2H)-yl)-N-methyl-N-phenylacetamide (7d) exhibited high binding affinity (Ki = 13.4 nM) with the TSPO and moderate lipophilicity (log D = 1.92). [18F]7d was radiosynthesized by [18F]fluorination of the bromopyridine precursor 7h with [18F]F- in 12 ± 5% radiochemical yield (n = 6, decay-corrected). In vitro autoradiography and PET studies of ischemic rat brain revealed higher binding of [18F]7d with TSPO on the ipsilateral side, as compared to the contralateral side, and improved brain kinetics compared with our previously developed radiotracers. Metabolite study of [18F]7d showed 93% of unchanged form in the ischemic brain at 30 min after injection. Moreover, PET study with [18F]7d provided a clear tumor image in a glioma-bearing rat model. We demonstrated that [18F]7d is a useful PET radiotracer for visualizing not only neuroinflammation but also glioma and will translate this radiotracer to a "first-in-human" study in our facility.