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
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.
1. Molecular Imaging Centre, National Institute of Radiological Sciences, Chiba, Japan.
Theranostics. 2015 May 26;5(9):961-9. doi: 10.7150/thno.12027. eCollection 2015.
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.
我们评估了2-5-(4-[(¹⁸)F]氟乙氧基-2-氧代-1,3-苯并恶唑-3(2H)-基)-N-甲基-N-苯基乙酰胺用于转运蛋白(18 kDa，TSPO)正电子发射断层扫描(PET)成像的效果。采用解剖法确定[(¹⁸)F]FEBMP在小鼠体内的分布，而小动物PET和代谢物分析则用于局灶性脑缺血大鼠模型。[(¹⁸)F]FEBMP在富含TSPO的小鼠外周器官中显示出高放射性摄取，并且初始脑摄取相对较高(2.67±0.12% ID/g)。PET成像显示梗死纹状体中的放射性积累增加，与未损伤纹状体相比，最大比值为3.20±0.12。用特异性TSPO配体进行置换可将梗死灶中的积累水平降低至对侧水平。这表明增加的积累反映了[(¹⁸)F]FEBMP在体内的TPSO特异性结合。使用简化参考组织模型，梗死区域的结合潜能为2.72±0.27。脑组织中的代谢物分析表明，在30分钟和60分钟时，分别有83.2±7.4%和76.4±2.1%的放射性来自完整的[(¹⁸)F]FEBMP，且该比例高于血浆中的比例(分别为8.6±1.9%和3.9±1.1%)。对死后人类大脑进行的体外放射自显影显示，TSPO rs6971多态性不影响[(¹⁸)F]FEBMP的结合位点。这些发现表明[(¹⁸)F]FEBMP是一种用于可视化神经炎症的有前景新工具。
Zotero 插件
