Visualization of acute liver damage induced by cycloheximide in rats using PET with [(18)F]FEDAC, a radiotracer for translocator protein (18 kDa).
Visualization of acute liver damage induced by cycloheximide in rats using PET with [(18)F]FEDAC, a radiotracer for translocator protein (18 kDa).
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DOI：
10.1371/journal.pone.0086625
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhang MR
中科院分区：
文献类型：
--
作者：
Hatori A;Yui J;Xie L;Yamasaki T;Kumata K;Fujinaga M;Wakizaka H;Ogawa M;Nengaki N;Kawamura K;Zhang MR
药物毒性引起的肝损伤是医生和患者都非常关注的问题。本研究的目的是使用N-苄基-N-甲基-2-[7，8-二氢-7-（三氟甲基）苯基]-N-甲基-N-苄基-N-甲基-N-苄基-N-甲基-N-（2-[18F]氟乙基）-8-氧代-2-苯基-9H-嘌呤-9-基]乙酰胺（[18F]FEDAC），一种特异于转运蛋白的放射性示踪剂（18 kDa，TSPO）作为炎症的生物标志物，并确定肝脏中富集TSPO表达的细胞来源。通过单次腹腔注射环己酰亚胺（CHX）制备大鼠轻度急性肝损伤模型。CHX处理诱导肝细胞凋亡和坏死变化，伴有轻度中性粒细胞浸润。注射[18 F]FEDAC后，用PET测量大鼠肝脏中的放射性摄取。与对照组相比，CHX治疗损伤的肝脏中[18 F]FEDAC的摄取增加。采用定量逆转录-聚合酶链反应和免疫组化方法检测肝组织中TSPO的存在。与对照组相比，受损肝脏中TSPO的mRNA表达升高，并且该水平与[18 F]FEDAC摄取和损伤严重程度相关。TSPO在受损肝脏切片中的表达主要见于巨噬细胞（枯否细胞）和中性粒细胞，而不在肝细胞中。TSPO mRNA表达的升高来源于损伤肝脏中具有TSPO的巨噬细胞和具有TSPO的中性粒细胞数量的增加。从这项研究中，我们认为，PET成像与[18 F]FEDAC代表轻度肝损伤，通过增强TSPO信号的炎症细胞。结论：该方法对急性肝损伤的早期诊断有一定价值。
Liver damage induced by drug toxicity is an important concern for both medical doctors and patients. The aim of this study was to noninvasively visualize acute liver damage using positron emission tomography (PET) with N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-[18F]fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide ([18F]FEDAC), a radiotracer specific for translocator protein (18 kDa, TSPO) as a biomarker for inflammation, and to determine cellular sources enriching TSPO expression in the liver. A mild acute liver damage model was prepared by a single intraperitoneal injection of cycloheximide (CHX) into rats. Treatment with CHX induced apoptosis and necrotic changes in hepatocytes with slight neutrophil infiltration. The uptake of radioactivity in the rat livers was measured with PET after injection of [18F]FEDAC. The uptake of [18F]FEDAC increased in livers damaged from treatment with CHX compared to the controls. Presence of TSPO was examined in the liver tissue using quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical assays. mRNA expression of TSPO was elevated in the damaged livers compared to the controls, and the level was correlated with the [18F]FEDAC uptake and severity of damage. TSPO expression in the damaged liver sections was mainly found in macrophages (Kupffer cells) and neutrophils, but not in hepatocytes. The elevation of TSPO mRNA expression was derived from the increase of the number of macrophages with TSPO and neutrophils with TSPO in damaged livers. From this study we considered that PET imaging with [18F]FEDAC represented the mild liver damage through the enhanced TSPO signal in inflammatory cells. We conclude that this method may be a useful tool for diagnosis in early stage of acute liver damage.
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影响因子：
13.5
作者：
Dhirapong, Amy;Yang, Guo-Xiang;Nadler, Steven;Zhang, Weici;Tsuneyama, Koichi;Leung, Patrick;Knechtle, Stuart;Ansari, Aftab A.;Coppel, Ross L.;Liu, Fu-Tong;He, Xiao-Song;Gershwin, M. Eric
通讯作者：
Gershwin, M. Eric
DOI：
10.1523/jneurosci.2312-08.2008
发表时间：
2008-11-19
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Ji B;Maeda J;Sawada M;Ono M;Okauchi T;Inaji M;Zhang MR;Suzuki K;Ando K;Staufenbiel M;Trojanowski JQ;Lee VM;Higuchi M;Suhara T
通讯作者：
Suhara T
影响因子：
--
作者：
Marino, G;Zimmerman, H J;Lewis, J H
通讯作者：
Lewis, J H
影响因子：
4.8
作者：
Giatzakis, C;Papadopoulos, V
通讯作者：
Papadopoulos, V
影响因子：
4.3
作者：
Kurosaka, K;Watanabe, N;Kobayashi, Y
通讯作者：
Kobayashi, Y