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

• Published in: Theranostics 2015-01, Vol.5 (9), p.961-969
• Main Authors: Tiwari, Anjani K, Ji, Bin, Yui, Joji, Fujinaga, Masayuki, Yamasaki, Tomoteru, Xie, Lin, Luo, Rui, Shimoda, Yoko, Kumata, Katsushi, Zhang, Yiding, Hatori, Akiko, Maeda, Jun, Higuchi, Makoto, Wang, Feng, Zhang, Ming-Rong
• Format: Article
• Language: English
• Subjects: Acetanilides - administration & dosage; Acetanilides - pharmacokinetics; Animals; Benzoxazoles - administration & dosage; Benzoxazoles - pharmacokinetics; Brain - diagnostic imaging; Brain - pathology; Brain Ischemia - diagnosis; Brain Ischemia - pathology; Carrier Proteins - analysis; Disease Models, Animal; Fluorine Radioisotopes - administration & dosage; Fluorine Radioisotopes - pharmacokinetics; Humans; Inflammation - diagnosis; Inflammation - pathology; Male; Mice; Neuroimaging - methods; Positron-Emission Tomography - methods; Radiography; Rats, Sprague-Dawley; Receptors, GABA - analysis; Receptors, GABA-A - analysis; Research Paper
• ISSN: 1838-7640; 1838-7640
• DOI: 10.7150/thno.12027

We evaluated the efficacy of 2-[5-(4-[(18)F]fluoroethoxy-2-oxo-1,3-benzoxazol-3(2H)-yl)-N-methyl-N-phenylacetamide] ([(18)F]FEBMP) for positron emission tomography (PET) imaging of translocator protein (18 kDa, TSPO). Dissection was used to determine the distribution of [(18)F]FEBMP in mice, while small-animal PET and metabolite analysis were used for a rat model of focal cerebral ischemia. [(18)F]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 [(18)F]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 [(18)F]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 [(18)F]FEBMP. These findings suggest that [(18)F]FEBMP is a promising new tool for visualization of neuroinflammation.