[18F]FEBMP: Positron Emission Tomography Imaging of TSPO in a Model of Neuroinflammation in Rats, and in vitro Autoradiograms of the Human Brain

We evaluated the efficacy of 2-[5-(4-[F-18]fluoroethoxy-2-oxo-1,3-benzoxazol-3(2H)-yl)-N-methyl-N-phenylacetamide] ([F-18]FEBMP) for positron emission tomography (PET) imaging of translocator protein (18 kDa, TSPO). Dissection was used to determine the distribution of [F-18]FEBMP in mice, while small-animal PET and metabolite analysis were used for a rat model of focal cerebral ischemia. [F-18]FEBMP showed high radioactivity uptake in mouse peripheral organs enriched with TSPO, and relatively high initial brain uptake (2.67 +/- 0.12% ID/g). PET imaging revealed an increased accumulation of radioactivity in the infarcted striatum, with a maximum ratio of 3.20 +/- 0.12, compared to non-injured striatum. Displacement with specific TSPO ligands lowered the accumulation levels in infarcts to those on the contralateral side. This suggests that the increased accumulation reflected TPSO-specific binding of [F-18]FEBMP in vivo. Using a simplified reference tissue model, the binding potential on the infarcted area was 2.72 +/- 0.27. Metabolite analysis in brain tissues showed that 83.2 +/- 7.4% and 76.4 +/- 2.1% of radioactivity was from intact [F-18]FEBMP at 30 and 60 min, respectively, and that this ratio was higher than in plasma (8.6 +/- 1.9% and 3.9 +/- 1.1%, respectively). In vitro autoradiography on postmortem human brains showed that TSPO rs6971 polymorphism did not affect binding sites for [F-18]FEBMP. These findings suggest that [F-18]FEBMP is a promising new tool for visualization of neuroinflammation.