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Lei Li, Wei Wang, Li-Ming Zhang, Xiang-Yun Jiang, Shu-Zheng Sun, Li-Jun Sun, Ying Guo, Jie Gong, You-Zhi Zhang, Heng-Lin Wang, Yun-Feng Li
The 18 kDa translocator protein (TSPO) is a five transmembrane domain protein that plays a crucial role in neurosteroid (e.g., allopregnanolone) synthesis by promoting the transport of cholesterol to the inner mitochondrial membrane. This protein is predominantly expressed in steroid-synthesizing tissues, including the central and peripheral nervous system, affecting stress-related disorders such as anxiety and depression. Recent studies have focused on the hippocampal dentate gyrus, which is very important for involvement of anxiety and depression...
June 24, 2017: Neuropharmacology
Xiang Kong, Song Luo, Jin Rong Wu, Shawn Wu, Carlo N De Cecco, U Joseph Schoepf, Adam J Spandorfer, Chun Yan Wang, Ying Tian, Hui Juan Chen, Guang Ming Lu, Gui Fen Yang, Long Jiang Zhang
Neuroinflammation is considered to be the pathogenesis of hepatic encephalopathy (HE), and imaging neuroinflammation is implicated in HE management. (11)C-PK11195, a typical translocator protein (TSPO) radiotracer, is used for imaging neuroinflammation. However, it has inherent limitations, such as short half-life and limited availability. The purpose of this study was to demonstrate the efficiency of new generation TSPO radiotracer, (18)F-DPA-714, in detecting and monitoring neuroinflammation of chronic HE...
2016: Theranostics
F Mattner, M Quinlivan, I Greguric, T Pham, X Liu, T Jackson, P Berghofer, C J R Fookes, B Dikic, M-C Gregoire, F Dolle, A Katsifis
The high affinity translocator protein (TSPO) ligand 6-chloro-2-(4'-iodophenyl)-3-(N,N-methylethyl)imidazo[1,2-a]pyridine-3-acetamide (CLINME) was radiolabelled with iodine-123 and assessed for its sensitivity for the TSPO in rodents. Moreover neuroinflammatory changes on a unilateral excitotoxic lesion rat model were detected using SPECT imaging. [(123)I]-CLINME was prepared in 70-80% radiochemical yield. The uptake of [(123)I]-CLINME was evaluated in rats by biodistribution, competition, and metabolite studies...
2015: Disease Markers
Anjani K Tiwari, Bin Ji, Joji Yui, Masayuki Fujinaga, Tomoteru Yamasaki, Lin Xie, Rui Luo, Yoko Shimoda, Katsushi Kumata, Yiding Zhang, Akiko Hatori, Jun Maeda, Makoto Higuchi, Feng Wang, Ming-Rong Zhang
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...
2015: Theranostics
Chiara Cerami, Daniela Perani
Neuroinflammation is a complex biological response to any injury occurring to the central nervous system. It is mainly characterized by the recruitment of immune system cells, namely the microglial cells, in the site of injury. Once activated, microglia expresses a cholesterol transporter protein (TSPO), previously also known as peripheral type benzodiazepine receptor. PK11195 is a ligand for TSPO and, labelled with a positron emitter, it is also the most used tracer for PET molecular imaging to in vivo map the microglia activation in various neurological disorders, including ischemic stroke...
2015: Current Vascular Pharmacology
Dennis O'Shea, Rabia Ahmad, Erik Årstad, Michelle Avory, Wai-Fung Chau, Clare Durrant, Ella Hirani, Paul A Jones, Imtiaz Khan, Sajinder K Luthra, Dimitrios Mantzilas, Véronique Morisson-Iveson, Joanna Passmore, Edward G Robins, Bo Shan, Harry Wadsworth, Sarah Walton, Yongjun Zhao, William Trigg
A series of novel TSPO ligands based on the tetracyclic class of translocator protein (TSPO) ligands first described by Okubo et al. was synthesised and evaluated as potential positron emitting tomography (PET) ligands for imaging TPSO in vivo. Fluorine-18 labelling of the molecules was achieved using direct radiolabelling or synthon based labelling approaches. Several of the ligands prepared have promising profiles as potential TSPO PET imaging ligands.
April 15, 2013: Bioorganic & Medicinal Chemistry Letters
Harry Wadsworth, Paul A Jones, Wai-Fung Chau, Clare Durrant, Véronique Morisson-Iveson, Joanna Passmore, Dennis O'Shea, Duncan Wynn, Imtiaz Khan, Andrew Black, Michelle Avory, William Trigg
A series of novel ligands based on the diaryl anilide (DAA) class of translocator protein (TSPO) ligands was synthesised and evaluated as potential positron emitting tomography (PET) ligands for imaging TPSO in vivo. Fluorine-18 labelling of the molecules was achieved using direct radiolabelling or synthon based labelling approaches. Several of the ligands prepared have promising profiles as potential TSPO PET imaging ligands and will be evaluated further as potential clinical imaging agents.
September 15, 2012: Bioorganic & Medicinal Chemistry Letters
Hsien-Hsin Chou, Ling-Yuan Hsu, Hwai-Tsu Hu
Digital images are often corrupted by impulsive noise during data acquisition, transmission, and processing. This paper presents a turbulent particle swarm optimization (PSO) (TPSO)-based fuzzy filtering (or TPFF for short) approach to remove impulse noise from highly corrupted images. The proposed fuzzy filter contains a parallel fuzzy inference mechanism, a fuzzy mean process, and a fuzzy composition process. To a certain extent, the TPFF is an improved and online version of those genetic-based algorithms which had attracted a number of works during the past years...
February 2013: IEEE Transactions on Cybernetics
L Rossard, F Favreau, J Demars, R Robert, C Nadeau, J Cau, R Thuillier, T Hauet
Renal failure due to ischemic injury is a common denominator of various clinical situations in critically ill patients. This study was designed to characterize the TPSO/Cholesterol synthesis and cell division pathways in response to different levels of ischemia. Porcine kidneys were subjected to either 60 min-warm ischemia (WI) or auto-transplanted after cold storage for 24 h at 4°C (CS), or both conditions (WI+CS), pathway activation and function were evaluated at 3 h, 3 and 7 days after reperfusion. CS combined to WI affects renal functions indicating a high degree of injury...
May 2012: Current Molecular Medicine
Christoforos Giatzakis, Amani Batarseh, Luis Dettin, Vassilios Papadopoulos
The translocator protein (18 kDa; TSPO), previously known as peripheral-type benzodiazepine receptor, is a high-affinity cholesterol- and drug-binding mitochondrial protein involved in various cell functions including steroidogenesis, apoptosis, and proliferation. TSPO is highly expressed in secretory and glandular tissues, especially in steroidogenic cells, and its expression is altered in certain pathological conditions such as cancer and neurological diseases. In this study, we characterized the regulatory elements present in the region of the TPSO promoter extending from 515 to 805 bp upstream of the transcription start site, an area previously identified as being important for transcription...
April 24, 2007: Biochemistry
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