| Autor: |
Tiwari AK; 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., Ji B; 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan., Yui J; 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan., Fujinaga M; 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan., Yamasaki T; 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan., Xie L; 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan., Luo R; 3. Department of Nuclear Medicine, Nanjing Hospital, Affiliated to Nanjing Medical University, Nanjing, China ., Shimoda Y; 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan., Kumata K; 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan., Zhang Y; 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan., Hatori A; 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan., Maeda J; 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan., Higuchi M; 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan., Wang F; 3. Department of Nuclear Medicine, Nanjing Hospital, Affiliated to Nanjing Medical University, Nanjing, China ., Zhang MR; 1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan. |
| Abstrakt: |
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. |
