(11)C-DPA-713 Versus (18)F-GE-180: A Preclinical Comparison of Translocator Protein 18 kDa PET Tracers to Visualize Acute and Chronic Neuroinflammation in a Mouse Model of Ischemic Stroke.
(11)C-DPA-713 Versus (18)F-GE-180: A Preclinical Comparison of Translocator Protein 18 kDa PET Tracers to Visualize Acute and Chronic Neuroinflammation in a Mouse Model of Ischemic Stroke.
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DOI：
10.2967/jnumed.118.209155
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发表时间：
2019-01
期刊：
影响因子：
--
通讯作者：
James ML
中科院分区：
文献类型：
--
作者：
Chaney A;Cropper HC;Johnson EM;Lechtenberg KJ;Peterson TC;Stevens MY;Buckwalter MS;James ML
神经炎症在缺血性脑卒中后神经元损伤中起关键作用。转运蛋白18kda （TSPO）的PET成像允许临床前和临床环境下神经炎症的纵向、无创可视化。许多TSPO示踪剂已经开发出来，然而，目前尚不清楚哪种示踪剂在监测神经炎症的体内时空动态方面最敏感和准确。因此，有必要对不同疾病状态下有前途的TSPO PET示踪剂进行正面比较。因此，本研究的目的是首次直接比较两种有前景的第二代TSPO示踪剂11C-DPA-713和18F-GE-180在缺血性脑卒中急性和慢性时间点的作用。方法：小鼠脑卒中后2、6、28 d分别用11C-DPA-713和18F-GE-180连续PET/CT成像。获得t2加权MR图像，以便描绘同侧（梗死）和对侧感兴趣的大脑区域（roi）。通过计算mr引导下roi中每克注射剂量的百分比来分析PET/CT图像。使用对侧丘脑（SUVTh）作为假参考区域来确定SUV比率。通过体外放射自显影和免疫组织化学来验证体内的发现。结果：使用11C-DPA-713和18F-GE-180在急性和慢性时间点观察到，与对侧ROI相比，同侧示踪剂摄取显著增加（SUVTh， 50-60分钟总数据）。离体放射自显像证实了在体内的发现，表明与对侧脑组织相比，梗死脑组织中TSPO示踪剂摄取增加。重要的是，小胶质细胞/巨噬细胞活化（分化簇68免疫染色）与11C-DPA-713- PET信号之间存在显著相关性，而在18F-GE-180中不明显。TSPO PET与活化的星形胶质细胞（胶质纤维酸性蛋白免疫染色）之间无显著相关性。结论：11C-DPA-713和18F-GE-180 PET可以检测小鼠脑缺血后急性和慢性时间点的神经炎症。11C-DPA-713 PET比18F-GE-180更准确地反映梗死小鼠大脑中远端动脉闭塞脑组织中小胶质细胞的激活程度，并显得略敏感。这些结果强调了11C-DPA-713在中风后体内追踪小胶质细胞激活的潜力，值得在临床前和临床环境中进一步研究。
Neuroinflammation plays a key role in neuronal injury after ischemic stroke. PET imaging of translocator protein 18 kDa (TSPO) permits longitudinal, noninvasive visualization of neuroinflammation in both preclinical and clinical settings. Many TSPO tracers have been developed, however, it is unclear which tracer is the most sensitive and accurate for monitoring the in vivo spatiotemporal dynamics of neuroinflammation across applications. Hence, there is a need for head-to-head comparisons of promising TSPO PET tracers across different disease states. Accordingly, the aim of this study was to directly compare 2 promising second-generation TSPO tracers, 11C-DPA-713 and 18F-GE-180, for the first time at acute and chronic time points after ischemic stroke. Methods: After distal middle cerebral artery occlusion or sham surgery, mice underwent consecutive PET/CT imaging with 11C-DPA-713 and 18F-GE-180 at 2, 6, and 28 d after stroke. T2-weighted MR images were acquired to enable delineation of ipsilateral (infarct) and contralateral brain regions of interest (ROIs). PET/CT images were analyzed by calculating percentage injected dose per gram in MR-guided ROIs. SUV ratios were determined using the contralateral thalamus (SUVTh) as a pseudoreference region. Ex vivo autoradiography and immunohistochemistry were performed to verify in vivo findings. Results: Significantly increased tracer uptake was observed in the ipsilateral compared with contralateral ROI (SUVTh, 50–60 min summed data) at acute and chronic time points using 11C-DPA-713 and 18F-GE-180. Ex vivo autoradiography confirmed in vivo findings demonstrating increased TSPO tracer uptake in infarcted versus contralateral brain tissue. Importantly, a significant correlation was identified between microglial/macrophage activation (cluster of differentiation 68 immunostaining) and 11C-DPA-713- PET signal, which was not evident with 18F-GE-180. No significant correlations were observed between TSPO PET and activated astrocytes (glial fibrillary acidic protein immunostaining). Conclusion: 11C-DPA-713 and 18F-GE-180 PET enable detection of neuroinflammation at acute and chronic time points after cerebral ischemia in mice. 11C-DPA-713 PET reflects the extent of microglial activation in infarcted distal middle cerebral artery occlusion mouse brain tissue more accurately than 18F-GE-180 and appears to be slightly more sensitive. These results highlight the potential of 11C-DPA-713 for tracking microglial activation in vivo after stroke and warrant further investigation in both preclinical and clinical settings.
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影响因子：
4.7
作者：
Chaney A;Bauer M;Bochicchio D;Smigova A;Kassiou M;Davies KE;Williams SR;Boutin H
通讯作者：
Boutin H
影响因子：
3
作者：
Doyle, Kristian P.;Fathali, Nancy;Siddiqui, Mohammad R.;Buckwalter, Marion S.
通讯作者：
Buckwalter, Marion S.
影响因子：
3.4
作者：
Jin, Rong;Liu, Lin;Zhang, Shihao;Nanda, Anil;Li, Guohong
通讯作者：
Li, Guohong
DOI：
10.1016/j.bbadis.2016.01.015
发表时间：
2016-05
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Kalaria RN;Akinyemi R;Ihara M
通讯作者：
Ihara M
影响因子：
3.3
作者：
Becker KJ;Tanzi P;Zierath D;Buckwalter MS
通讯作者：
Buckwalter MS