Theranostics 2015; 5(9):961-969. doi:10.7150/thno.12027

Research Paper

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

Anjani K. Tiwari*,1,2, Bin Ji*,1, Joji Yui1, Masayuki Fujinaga1, Tomoteru Yamasaki1, Lin Xie1, Rui Luo3, Yoko Shimoda1, Katsushi Kumata1, Yiding Zhang1, Akiko Hatori1, Jun Maeda1, Makoto Higuchi1, Feng Wang3, ✉, Ming-Rong Zhang1, ✉

1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan
2. Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, India
3. Department of Nuclear Medicine, Nanjing Hospital, Affiliated to Nanjing Medical University, Nanjing, China.
*These authors contributed equally to this work

Abstract

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

Keywords: [18F]FEBMP, translocator protein (18 kDa), neuroinflammation, binding potential, rs6971 polymorphism

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How to cite this article:
Tiwari AK, Ji B, Yui J, Fujinaga M, Yamasaki T, Xie L, Luo R, Shimoda Y, Kumata K, Zhang Y, Hatori A, Maeda J, Higuchi M, Wang F, Zhang MR. [18F]FEBMP: Positron Emission Tomography Imaging of TSPO in a Model of Neuroinflammation in Rats, and in vitro Autoradiograms of the Human Brain. Theranostics 2015; 5(9):961-969. doi:10.7150/thno.12027. Available from http://www.thno.org/v05p0961.htm