Kong Xiang, Luo Song, Wang Yun Fei, Yang Gui Fen, Lu Guang Ming, Zhang Long Jiang
Department of Diagnostic Radiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
Department of Nuclear Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
Front Neurosci. 2021 Aug 16;15:678144. doi: 10.3389/fnins.2021.678144. eCollection 2021.
Neuroinflammation is an important pathogenesis of hepatic encephalopathy (HE). The upregulation of translocator protein (TSPO) during neuroinflammation provides an imaging molecular target to evaluate the severity of neuroinflammation in chronic HE rats. [18F]DPA-714 and [18F]PBR146 targeting TSPO are often used for neuroinflammation imaging. This study performed bile duct ligation (BDL) in rats to simulate chronic HE model, tested the behavioral experiments, and conducted [18F]PBR146 and [18F]DPA-714 micro-PET/CT scans followed analyzing the average %ID/g values of the whole brain, brain regions and main organs of subjects. After sacrifice the rats, the blood plasma samples were taken for blood biochemical indexes and plasma inflammatory factor levels examination, the liver and brain specimens were obtained for pathological analysis. The BDL rats showed chronic liver failure with defects in cognition, motor coordination ability and mental state. [18F]PBR146 and [18F]DPA-714 micro-PET/CT imaging results were similar in whole brain of BDL group and Sham group. Besides, some regional brain areas in BDL rats were found abnormal uptakes mainly located in basal ganglia area, auditory cortex, motor cortex, cingulate gyrus, somatosensory cortex, hippocampus, thalamus, midbrain, and medulla oblongata, and these regions also correlated with behavioral alterations. In conclusion, both [18F]PBR146 and [18F]DPA-714 had the similar imaging effects in hepatic encephalopathy models could quantitatively evaluate neuroinflammation load and distribution. The difference brain regions with higher uptake values of radiotracers in BDL rats were correlated with behavioral alterations.
神经炎症是肝性脑病（HE）的重要发病机制。神经炎症过程中转位蛋白（TSPO）的上调为评估慢性HE大鼠神经炎症的严重程度提供了一个成像分子靶点。靶向TSPO的[18F]DPA - 714和[18F]PBR146常用于神经炎症成像。本研究对大鼠进行胆管结扎（BDL）以模拟慢性HE模型，进行行为实验，并在分析受试者全脑、脑区和主要器官的平均%ID/g值后进行[18F]PBR146和[18F]DPA - 714微PET/CT扫描。处死大鼠后，采集血浆样本检测血液生化指标和血浆炎症因子水平，获取肝脏和脑标本进行病理分析。BDL大鼠表现出慢性肝功能衰竭，伴有认知、运动协调能力和精神状态缺陷。BDL组和假手术组全脑的[18F]PBR146和[18F]DPA - 714微PET/CT成像结果相似。此外，发现BDL大鼠一些脑区存在异常摄取，主要位于基底神经节区、听觉皮层、运动皮层、扣带回、体感皮层、海马、丘脑、中脑和延髓，且这些区域也与行为改变相关。总之，[18F]PBR146和[18F]DPA - 714在肝性脑病模型中具有相似的成像效果，可定量评估神经炎症负荷及分布。BDL大鼠中放射性示踪剂摄取值较高的差异脑区与行为改变相关。
