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https://www.readbyqxmd.com/read/28302760/-11-c-pbr28-or-18-f-pbr111-detect-white-matter-inflammatory-heterogeneity-in-multiple-sclerosis
#1
Gourab Datta, Alessandro Colasanti, Nicola Kalk, David R Owen, Gregory Scott, Eugenii Ilan A Rabiner, Roger Gunn, Anne Lingford-Hughes, Omar Malik, Olga Ciccarelli, Richard Nicholas, Lei Nie, Marco Battaglini, Nicola De Stefano, Paul Matthews
Objective: To assess microglial activation in lesions and in normal appearing white matter of multiple sclerosis (MS) patients using positron emission tomography (PET). Methods: 34 MS patients (7 with secondary progressive MS (SPMS), 27 with relapsing remitting MS (RRMS)) and 30 healthy volunteers, genetically stratified for translocator protein (TSPO), binding status underwent PET scanning with TSPO radioligands ((11)C-PBR28 or (18)F-PBR111). Regional TSPO availability was measured as a distribution volume ratio (DVR) relative to the caudate (a pseudo-reference region)...
March 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28285077/multilayer-photodynamic-therapy-for-highly-effective-and-safe-cancer-treatment
#2
Ling Yang, Shaojuan Zhang, Xiaoxi Ling, Pin Shao, Ningyang Jia, Mingfeng Bai
Recent efforts to develop tumor-targeted photodynamic therapy (PDT) photosensitizers (PSs) have greatly advanced the potential of PDT in cancer therapy, although complete eradication of tumor cells by PDT alone remains challenging. As a way to improve PDT efficacy, we report a new combinatory PDT therapy technique that specifically targets multilayers of cells. Simply mixing different PDT PSs, even those that target distinct receptors (this may still lead to similar cell-killing pathways), may not achieve ideal therapeutic outcomes...
March 8, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28283959/neuroinflammation-in-neurodegenerative-disorders-a-review
#3
REVIEW
Martin Schain, William Charles Kreisl
The potential for positron emission tomography (PET) to detect neuroinflammation in vivo has sparked a remarkable interest in various disciplines of neuroscience. Early PET radioligands, such as [(11)C]PK(R)-11195 for the 18-kDa translocator protein (TSPO) and [(11)C]L-deprenyl for monoamine oxidase B, have been used in studies designed to clarify the role of neuroinflammation in a variety of psychiatric and neurological disorders. Recent years have witnessed the development of several second-generation PET radioligands for TSPO and radioligands to measure endogenous targets that are active in various stages of the inflammatory cascade, such as cyclooxygenase and arachidonic acid...
March 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28277971/distinct-light-stress-and-nutrient-dependent-regulation-of-multiple-tryptophan-rich-sensory-protein-tspo-genes-in-the-cyanobacterium-fremyella-diplosiphon
#4
Andrea W U Busch, Beronda L Montgomery
The cyanobacterium Fremyella diplosiphon possesses 3 genes encoding homologs of the tryptophan-rich sensory protein (TSPO). TSPO proteins are membrane proteins implicated in stress responses across a range of organisms from bacteria to humans. Diverse TSPO proteins appear to generally bind tetrapyrrole ligands. Previously, we reported that one of these homologs, FdTSPO1, is involved in salt-, osmotic- and oxidative stress responses in F. diplosiphon. Here, we show distinct regulation of cellular mRNA levels of all 3 FdTSPO homologs by different abiotic stresses...
March 4, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28267890/modified-benzoxazolone-derivative-as-18-kda-tspo-ligand
#5
Neelam Kumari, Nidhi Chadha, Pooja Srivastava, Lokesh Chandra Mishra, Sunita Bhagat, Anil K Mishra, Anjani K Tiwari
We have synthesized six new congeners of acetamido-benzoxazolone for Translocator Protein [18 kDa, TSPO] imaging. The best in vitro binding affinity (10.8 ± 1.2 nM) for TSPO was found for N-methyl-2-(5-(naphthalen-1-yl)-2-oxobenzo[d]oxazol-3(2H)-yl)-N-phenylacetamide, (NBMP). NBMP was synthesised by suzuki coupling reaction between 2-(5-bromo-2-oxo-1,3-benzoxazol-3(2H)-yl)-N-phenylacetamide and napthalene-1-boronic acid. Computational docking and simulation studies showed not much impact of intersubject variability on binding which is one of the major drawbacks of several TSPO ligands...
March 7, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28263860/subcellular-distribution-of-the-18kda-translocator-protein-and-transcript-variant-pbr-s-in-human-cells
#6
Guo-Jun Liu, Ryan J Middleton, Richard B Banati
Despite continued interest in the 18kDa translocator protein (PBR/TSPO) as a biomarker and a therapeutic target for a range of diseases, its functional role, such as in the steroid synthesis pathway and energy metabolism has either become contentious or remains to be described more precisely. The PBR/TSPO gene consists of four exons, while a shorter isoform termed PBR-S lacks exon 2. The PBR-S 102-codon open reading frame differs to that of PBR/TSPO, resulting in a protein that is completely unrelated to PBR/TSPO...
March 2, 2017: Gene
https://www.readbyqxmd.com/read/28262740/effect-of-cigarette-smoking-on-a-marker-for-neuroinflammation-a-11-c-daa1106-positron-emission-tomography-study
#7
Arthur L Brody, Robert Hubert, Ryutaro Enoki, Lizette Y Garcia, Michael S Mamoun, Kyoji Okita, Edythe D London, Erika L Nurmi, Lauren C Seaman, Mark A Mandelkern
In the brain, microglia continuously scan the surrounding extracellular space, in order to respond to damage or infection by becoming activated and participating in neuroinflammation. When activated, microglia increase the expression of the translocator protein (TSPO) 18 kDa, thereby making TSPO expression a marker for neuroinflammation. We used the radiotracer [(11)C]DAA1106 (a ligand for TSPO) and positron emission tomography (PET) to determine the effect of smoking on availability of this marker for neuroinflammation...
March 6, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28245513/brain-translocator-protein-occupancy-by-ono-2952-in-healthy-adults-a-phase-1-pet-study-using-11-c-pbr28
#8
William G Frankle, Rajesh Narendran, Andrew T Wood, Fumitaka Suto, Michael L Himes, Michiyoshi Kobayashi, Tomoya Ohno, Akinori Yamauchi, Katsukuni Mitsui, Kevin Duffy, Bruce Mark
ONO-2952, a novel antagonist of translocator protein 18 kDa (TSPO), binds with high affinity to TSPO in rat brain and human tumor cell line membrane preparations. This study used the TSPO-specific PET radioligand [(11) C]PBR28 to confirm binding of ONO-2952 to brain TSPO in human subjects, and evaluate brain TSPO occupancy and its relationship with ONO-2952 plasma concentration. Sixteen healthy subjects received a single oral dose of 200, 60, 20, or 6 mg ONO-2952 (n=4 per dose). Two PET scans with [(11) C]PBR28 were conducted ≤7 days apart: at baseline and 24 hours after ONO-2952 administration...
February 28, 2017: Synapse
https://www.readbyqxmd.com/read/28242869/in-vivo-imaging-of-translocator-protein-a-marker-of-activated-microglia-in-alcohol-dependence
#9
A T Hillmer, C M Sandiego, J Hannestad, G A Angarita, A Kumar, E M McGovern, Y Huang, K C O'Connor, R E Carson, S S O'Malley, K P Cosgrove
Neuroinflammation may be a critical component of the neurobiology of alcohol use disorders, yet the exact nature of this relationship is not well understood. This work compared the brain and peripheral immune profile of alcohol-dependent subjects and controls. Brain levels of 18-kDa translocator protein (TSPO), a marker of microglial activation and neuroinflammation, were measured with [(11)C]PBR28 positron emission tomography imaging in 15 healthy controls and 15 alcohol-dependent subjects. Alcohol-dependent subjects were imaged 1-4 days (n=14) or 24 days (n=1) after their last drink...
February 28, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28235666/identification-of-novel-anti-cancer-agents-by-applying-insilico-methods-for-inhibition-of-tspo-protein
#10
Manan Bhargavi, Sree Kanth Sivan, Sarita Rajender Potlapally
Cancer is a genomic disease characterised as impaired cellular energy metabolism. Cancer cells derive most of their energy from oxidative phosphorylation unlike normal ones during cell progression TSPO protein present in external mitochondrial membrane, is involved in various cellular functions like Cell proliferation, mitochondrial respiration, synthesis of steroids and also participates in import of cholesterol into the inner mitochondrial membrane from outside of the membrane of mitochondria. The 3D model of TSPO protein is built using comparative homology modelling techniques and validated by proSA, Ramachandran plot and ERRAT in the present work...
February 14, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28219319/biomarkers-in-alzheimer-s-disease-recent-update
#11
Sushil Sharma, Walter Lipincott
Alzheimer disease (AD) is an age-related neurodegenerative disorder, characterized by loss of memory and cognitive function. It is the common cause of dementia in elderly and is a global health concern as the population of people aged 85 and older, is growing alarmingly. Although pharmacotherapy for the treatment of AD has improved, lot of work remains to treat this devastating disease. AD pathology begins even before the onset of clinical symptoms. Because therapies could be more effective if implemented early in the disease progression, it is highly prudent to discover reliable biomarkers, to detect its exact pathophysiology during pre-symptomatic stage...
February 20, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28194003/lower-levels-of-the-glial-cell-marker-tspo-in-drug-naive-first-episode-psychosis-patients-as-measured-using-pet-and-11-c-pbr28
#12
K Collste, P Plavén-Sigray, H Fatouros-Bergman, P Victorsson, M Schain, A Forsberg, N Amini, S Aeinehband, S Erhardt, C Halldin, L Flyckt, L Farde, S Cervenka
Several lines of evidence are indicative of a role for immune activation in the pathophysiology of schizophrenia. Nevertheless, studies using positron emission tomography (PET) and radioligands for the translocator protein (TSPO), a marker for glial activation, have yielded inconsistent results. Whereas early studies using a radioligand with low signal-to-noise in small samples showed increases in patients, more recent studies with improved methodology have shown no differences or trend-level decreases. Importantly, all patients investigated thus far have been on antipsychotic medication, and as these compounds may dampen immune cell activity, this factor limits the conclusions that can be drawn...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28156095/optimized-translocator-protein-ligand-for-optical-molecular-imaging-and-screening
#13
Jun Li, Jarrod A Smith, Eric S Dawson, Allie Fu, Michael L Nickels, Michael L Schulte, H Charles Manning
Translocator protein (TSPO) is a validated target for molecular imaging of a variety of human diseases and disorders. Given its involvement in cholesterol metabolism, TSPO expression is commonly elevated in solid tumors, including glioma, colorectal cancer, and breast cancer. TSPO ligands capable of detection by optical imaging are useful molecular tracers for a variety of purposes that range from quantitative biology to drug discovery. Leveraging our prior optimization of the pyrazolopyrimidine TSPO ligand scaffold for cancer imaging, we report herein a new generation of TSPO tracers with superior binding affinity and suitability for optical imaging and screening...
February 13, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28137769/combined-pet-imaging-of-the-inflammatory-tumor-microenvironment-identifies-margins-of-unique-radiotracer-uptake
#14
Bastian Zinnhardt, Hayet Pigeon, Benoit Thézé, Thomas Viel, Lydia Wachsmuth, Inga B Fricke, Sonja Schelhaas, Lisa Honold, Katrin Schwegmann, Stefan Wagner, Andreas Faust, Cornelius Faber, Michael T Kuhlmann, Sven Hermann, Michael Schäfers, Alexandra Winkeler, Andreas H Jacobs
The tumor microenvironment is highly heterogeneous. For gliomas, the tumor-associated inflammatory response is pivotal to support growth and invasion. Factors of glioma growth, inflammation, and invasion, such as the translocator protein (TSPO) and matrix metalloproteinases (MMP), may serve as specific imaging biomarkers of the glioma microenvironment. In this study, non-invasive imaging by positron emission tomography (PET) with [(18)F]DPA-714 (TSPO) and [(18)F]BR-351 (MMP) was used for assessment of localization and quantification of the expression of TSPO and MMP...
January 30, 2017: Cancer Research
https://www.readbyqxmd.com/read/28129443/anxiolytic-effects-of-hippocampal-neurosteroids-in-normal-and-neuropathic-rats-with-spared-nerve-injury
#15
Meng Zhang, Jia Liu, Meng-Meng Zhou, Honghai Wu, Yanning Hou, Yun-Feng Li, Yuxin Yin, Lemin Zheng, Jie Cai, Fei-Fei Liao, Feng-Yu Liu, Ming Yi, You Wan
Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of GABAA receptors, which play a vital role in modulating hippocampal functions. Chronic pain is accompanied by increased neurosteroid production in the spinal cord and thalamus. We hypothesize that hippocampal neurosteroids participate in pain or pain-associated emotions, which we tested with high-performance liquid chromatography/tandem mass spectrometry and pharmacological behavioral tests...
January 27, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28128020/positron-emission-tomography-of-cerebral-angiogenesis-and-tspo-expression-in-a-mouse-model-of-chronic-hypoxia
#16
Iwao Kanno, Chie Seki, Hiroyuki Takuwa, Zhao-Hui Jin, Didier Boturyn, Pascal Dumy, Takako Furukawa, Tsuneo Saga, Hiroshi Ito, Kazuto Masamoto
The present study aimed to examine whether positron emission tomography (PET) could evaluate cerebral angiogenesis. Mice were housed in a hypoxic chamber with 8-9% oxygen for 4, 7, and 14 days, and the angiogenic responses were evaluated with a radiotracer, (64)Cu-cyclam-RAFT-c(-RGDfK-)4, which targeted αVβ3 integrin and was imaged with PET. The PET imaging results showed little uptake during all of the hypoxic periods. Immunofluorescence staining of the β3 integrin, CD61, revealed weak expression, while the microvessel density assessed by CD31 staining increased with the hypoxic duration...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28108322/effect-of-zbd-2-on-chronic-pain-depressive-like-behaviors-and-recovery-of-motor-function-following-spinal-cord-injury-in-mice
#17
Xiao-Ming Li, Jia Meng, Lin Tao Li, Ting Guo, Liu-Kun Yang, Qi-Xin Shi, Xu-Bo Li, Yong Chen, Qi Yang, Jian-Ning Zhao
In addition to debilitating sensory and motor deficits, patients with spinal cord injury (SCI) may experience chronic hyperpathic pain (SCI-pain). Recent studies have revealed that translocator protein (TSPO) is involved in repairing neural cells as well as reducing anxiety and depression. However, the role of TSPO in SCI-pain and pain-induced depression remains unknown. The present study aimed to determine the effects of a new TSPO ligand, ZBD-2, on SCI-pain and consequent pain-induced depressive-like behaviors in mice...
March 30, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28103888/photoreceptor-protection-via-blockade-of-bet-epigenetic-readers-in-a-murine-model-of-inherited-retinal-degeneration
#18
Lei Zhao, Jun Li, Yingmei Fu, Mengxue Zhang, Bowen Wang, Jonathan Ouellette, Pawan K Shahi, Bikash R Pattnaik, Jyoti J Watters, Wai T Wong, Lian-Wang Guo
BACKGROUND: The bromodomain and extraterminal domain (BET) family proteins (BET2, BET3, and BET4) "read" (bind) histone acetylation marks via two distinct bromodomains (Brom1 and Brom2) facilitating transcriptional activation. These epigenetic "readers" play crucial roles in pathogenic processes such as inflammation. The role of BETs in influencing the degenerative process in the retina is however unknown. METHODS: We employed the rd10 mouse model (Pde6b (rd10) mutation) of retinitis pigmentosa (RP) to examine the involvement of BET proteins in retinal neurodegeneration...
January 19, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28103132/functional-gains-in-energy-and-cell-metabolism-after-tspo-gene-insertion
#19
Guo-Jun Liu, Ryan J Middleton, Winnie Wai-Ying Kam, David Y Chin, Claire R Hatty, Ronald H Y Chan, Richard B Banati
Recent loss-of-function studies in tissue-specific as well as global Tspo (Translocator Protein 18 kDa) knockout mice have not confirmed its long assumed indispensability for the translocation of cholesterol across the mitochondrial inter-membrane space, a rate-limiting step in steroid biosynthesis. Instead, recent studies in global Tspo knockout mice indicate that TSPO may play a more fundamental role in cellular bioenergetics, which may include the indirect down-stream regulation of transport or metabolic functions...
January 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28093569/translational-evaluation-of-translocator-protein-as-a-marker-of-neuroinflammation-in-schizophrenia
#20
T Notter, J M Coughlin, T Gschwind, U Weber-Stadlbauer, Y Wang, M Kassiou, A C Vernon, D Benke, M G Pomper, A Sawa, U Meyer
Positron emission tomography (PET) imaging with radiotracers that target translocator protein 18 kDa (TSPO) has become a popular approach to assess putative neuroinflammatory processes and associated microglia activation in psychotic illnesses. It remains unclear, however, whether TSPO imaging can accurately capture low-grade inflammatory processes such as those present in schizophrenia and related disorders. Therefore, we evaluated the validity of TSPO as a disease-relevant marker of inflammation using a translational approach, which combined neurodevelopmental and neurodegenerative mouse models with PET imaging in patients with recent-onset schizophrenia and matched controls...
January 17, 2017: Molecular Psychiatry
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