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PK11195 microglia

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https://www.readbyqxmd.com/read/27733171/persistent-neuroinflammation-and-cognitive-impairment-in-a-rat-model-of-acute-diisopropylfluorophosphate-intoxication
#1
Brenna M Flannery, Donald A Bruun, Douglas J Rowland, Christopher N Banks, Adam T Austin, David L Kukis, Yonggang Li, Byron D Ford, Daniel J Tancredi, Jill L Silverman, Simon R Cherry, Pamela J Lein
BACKGROUND: Acute intoxication with organophosphorus (OP) cholinesterase inhibitors can trigger convulsions that progress to life-threatening status epilepticus. Survivors face long-term morbidity including mild-to-severe decline in memory. It is posited that neuroinflammation plays a key role in the pathogenesis of OP-induced neuropsychiatric deficits. Rigorous testing of this hypothesis requires preclinical models that recapitulate relevant phenotypic outcomes. Here, we describe a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP) that exhibits persistent neuroinflammation and cognitive impairment...
October 12, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27602389/in-vivo-r-11-c-pk11195-pet-imaging-of-18kda-translocator-protein-in-recent-onset-psychosis
#2
Thalia F van der Doef, Lot D de Witte, Arjen L Sutterland, Ellen Jobse, Maqsood Yaqub, Ronald Boellaard, Lieuwe de Haan, Jonas Eriksson, Adriaan A Lammertsma, René S Kahn, Bart N M van Berckel
Evidence is accumulating that immune dysfunction is involved in the pathophysiology of schizophrenia. It has been hypothesized that microglia activation is present in patients with schizophrenia. Various in vivo and post-mortem studies have investigated this hypothesis, but as yet with inconclusive results. Microglia activation is associated with elevations in 18 kDa translocator protein (TSPO) levels, which can be measured with the positron emission tomography (PET) tracer (R)-[(11)C]PK11195. The purpose of the present study was to investigate microglia activation in psychosis in vivo at an early stage of the disease...
2016: NPJ Schizophrenia
https://www.readbyqxmd.com/read/27381824/quantitative-longitudinal-imaging-of-activated-microglia-as-a-marker-of-inflammation-in-the-pilocarpine-rat-model-of-epilepsy-using-11c-r-pk11195-pet-and-mri
#3
J Yankam Njiwa, N Costes, C Bouillot, S Bouvard, S Fieux, G Becker, E Levigoureux, G Kocevar, C Stamile, J B Langlois, R Bolbos, C Bonnet, L Bezin, L Zimmer, A Hammers
Inflammation may play a role in the development of epilepsy after brain insults. [(11)C]-(R)-PK11195 binds to TSPO, expressed by activated microglia. We quantified [(11)C]-(R)-PK11195 binding during epileptogenesis after pilocarpine-induced status epilepticus (SE), a model of temporal lobe epilepsy.Nine male rats were studied thrice (D0-1, D0 + 6, D0 + 35, D0 = SE induction). In the same session, 7T T2-weighted images and DTI for mean diffusivity (MD) and fractional anisotropy (FA) maps were acquired, followed by dynamic PET/CT...
July 5, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27340650/tspo-imaging-in-parkinsonian-disorders
#4
Alexander Gerhard
Microglial activation is a key aspect of the neuroinflammatory process in neurodegenerative disorders including idiopathic and atypical parkinsonian disorders. With positron emission tomography (PET) it has become possible to image this phenomenon in vivo and over the last years patterns of microglia activation corresponding with the known distribution of neuropathological changes in these disorders have been demonstrated using this technique. In addition the effects of interventions aimed at suppressing microglia activation as part of interventional trials have successfully been demonstrated...
2016: Clinical and Translational Imaging: Reviews in Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27279913/-18-f-dpa-714-pet-imaging-for-detecting-neuroinflammation-in-rats-with-chronic-hepatic-encephalopathy
#5
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
https://www.readbyqxmd.com/read/27117856/depiction-of-microglial-activation-in-aging-and-dementia-positron-emission-tomography-with-11c-dpa713-versus-11c-r-pk11195
#6
Masamichi Yokokura, Tatsuhiro Terada, Tomoyasu Bunai, Kyoko Nakaizumi, Kiyokazu Takebayashi, Yasuhide Iwata, Etsuji Yoshikawa, Masami Futatsubashi, Katsuaki Suzuki, Norio Mori, Yasuomi Ouchi
The presence of activated microglia in the brains of healthy elderly people is a matter of debate. We aimed to clarify the degree of microglial activation in aging and dementia as revealed by different tracers by comparing the binding potential (BPND) in various brain regions using a first-generation translocator protein (TSPO) tracer [(11)C](R)PK11195 and a second-generation tracer [(11)C]DPA713. The BPND levels, estimated using simplified reference tissue models, were compared among healthy young and elderly individuals and patients with Alzheimer's disease (AD) and were correlated with clinical scores...
April 26, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/26969181/changes-in-binding-of-123-i-clinde-a-high-affinity-translocator-protein-18%C3%A2-kda-tspo-selective-radioligand-in-a-rat-model-of-traumatic-brain-injury
#7
Cornelius K Donat, Khaled Gaber, Jürgen Meixensberger, Peter Brust, Lars H Pinborg, Henrik H Hansen, Jens D Mikkelsen
After traumatic brain injury (TBI), secondary injuries develop, including neuroinflammatory processes that contribute to long-lasting impairments. These secondary injuries represent potential targets for treatment and diagnostics. The translocator protein 18 kDa (TSPO) is expressed in activated microglia cells and upregulated in response to brain injury and therefore a potential biomarker of the neuroinflammatory processes. Second-generation radioligands of TSPO, such as [(123)I]CLINDE, have a higher signal-to-noise ratio as the prototype ligand PK11195...
June 2016: Neuromolecular Medicine
https://www.readbyqxmd.com/read/26959396/in-vivo-imaging-of-microglial-activation-by-positron-emission-tomography-with-11-c-pbr28-in-the-5xfad-model-of-alzheimer-s-disease
#8
Nazanin Mirzaei, Sac Pham Tang, Sharon Ashworth, Christopher Coello, Christophe Plisson, Jan Passchier, Vimal Selvaraj, Robin J Tyacke, David J Nutt, Magdalena Sastre
Microglial activation has been linked with deficits in neuronal function and synaptic plasticity in Alzheimer's disease (AD). The mitochondrial translocator protein (TSPO) is known to be upregulated in reactive microglia. Accurate visualization and quantification of microglial density by PET imaging using the TSPO tracer [(11)C]-R-PK11195 has been challenging due to the limitations of the ligand. In this study, it was aimed to evaluate the new TSPO tracer [(11)C]PBR28 as a marker for microglial activation in the 5XFAD transgenic mouse model of AD...
June 2016: Glia
https://www.readbyqxmd.com/read/26923911/transcranial-direct-current-stimulation-accelerates-recovery-of-function-induces-neurogenesis-and-recruits-oligodendrocyte-precursors-in-a-rat-model-of-stroke
#9
Ramona Braun, Rebecca Klein, Helene Luise Walter, Maurice Ohren, Lars Freudenmacher, Kaleab Getachew, Anne Ladwig, Joachim Luelling, Bernd Neumaier, Heike Endepols, Rudolf Graf, Mathias Hoehn, Gereon Rudolf Fink, Michael Schroeter, Maria Adele Rueger
BACKGROUND: Clinical data suggest that transcranial direct current stimulation (tDCS) may be used to facilitate rehabilitation after stroke. However, data are inconsistent and the neurobiological mechanisms underlying tDCS remain poorly explored, impeding its implementation into clinical routine. In the healthy rat brain, tDCS affects neural stem cells (NSC) and microglia. We here investigated whether tDCS applied after stroke also beneficially affects these cells, which are known to be involved in regeneration and repair...
May 2016: Experimental Neurology
https://www.readbyqxmd.com/read/26823567/pharmacokinetic-analysis-of-11c-pbr28-in-the-rat-model-of-herpes-encephalitis-comparison-with-r-11c-pk11195
#10
Andrea Parente, Paula Kopschina Feltes, David Vállez García, Jurgen W A Sijbesma, Cristina M Moriguchi Jeckel, Rudi A J O Dierckx, Erik F J de Vries, Janine Doorduin
(11)C-PBR28 is a second-generation translocator protein (TSPO) tracer with characteristics supposedly superior to the most commonly used tracer for neuroinflammation, (R)-(11)C-PK11195. Despite its use in clinical research, no studies on the imaging properties and pharmacokinetic analysis of (11)C-PBR28 in rodent models of neuroinflammation have been published yet. Therefore, this study aimed to evaluate (11)C-PBR28 as a tool for detection and quantification of neuroinflammation in preclinical research and to compare its imaging properties with (R)-(11)C-PK11195...
May 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/26697963/imaging-microglial-activation-with-tspo-pet-lighting-up-neurologic-diseases
#11
REVIEW
Lucy Vivash, Terence J O'Brien
Neuroinflammation is implicated in the pathogenesis of a wide range of neurologic and neuropsychiatric diseases. For over 20 years, (11)C-PK11195 PET, which aims to image expression of the translocator protein (TSPO) on activated microglia in the brain, has been used in preclinical and clinical research to investigate neuroinflammation in vivo in patients with brain diseases. However, (11)C-PK11195 suffers from two major limitations: its low brain permeability and high nonspecific and plasma binding results in a low signal-to-noise ratio, and the use of (11)C restricts its use to PET research centers and hospitals with an on-site cyclotron...
February 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/26551697/the-methodology-of-tspo-imaging-with-positron-emission-tomography
#12
REVIEW
Federico E Turkheimer, Gaia Rizzo, Peter S Bloomfield, Oliver Howes, Paolo Zanotti-Fregonara, Alessandra Bertoldo, Mattia Veronese
The 18-kDA translocator protein (TSPO) is consistently elevated in activated microglia of the central nervous system (CNS) in response to a variety of insults as well as neurodegenerative and psychiatric conditions. It is therefore a target of interest for molecular strategies aimed at imaging neuroinflammation in vivo. For more than 20 years, positron emission tomography (PET) has allowed the imaging of TSPO density in brain using [(11)C]-(R)-PK11195, a radiolabelled-specific antagonist of the TSPO that has demonstrated microglial activation in a large number pathological cohorts...
August 2015: Biochemical Society Transactions
https://www.readbyqxmd.com/read/26348581/volume-metabolites-and-neuroinflammation-of-the-hippocampus-in-bipolar-disorder-a-combined-magnetic-resonance-imaging-and-positron-emission-tomography-study
#13
Bartholomeus C M 'Benno' Haarman, Huibert Burger, Janine Doorduin, Remco J Renken, Anita J Sibeijn-Kuiper, Jan-Bernard C Marsman, Erik F J de Vries, Jan Cees de Groot, Hemmo A Drexhage, Richard Mendes, Willem A Nolen, Rixt F Riemersma-Van der Lek
BACKGROUND: The hippocampus is one of the brain regions that is involved in several pathophysiological theories about bipolar disorder (BD), such as the neuroinflammation theory and the corticolimbic metabolic dysregulation theory. We compared hippocampal volume and hippocampal metabolites in bipolar I disorder (BD-I) patients versus healthy controls (HCs) with magnetic resonance imaging (MRI) and spectroscopy (MRS). We post hoc investigated whether hippocampal volume and hippocampal metabolites were associated with microglial activation and explored if potential illness modifying factors affected these hippocampal measurements and whether these were associated with experienced mood and functioning...
August 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/26199457/radiosynthesis-in-vivo-biological-evaluation-and-imaging-of-brain-lesions-with-123i-clinme-a-new-spect-tracer-for-the-translocator-protein
#14
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
https://www.readbyqxmd.com/read/26067626/widespread-microglial-activation-in-patients-deceased-from-traumatic-brain-injury
#15
Antonio Velázquez, Marisa Ortega, Santiago Rojas, Francisco Javier González-Oliván, Alfonso Rodríguez-Baeza
PRIMARY OBJECTIVE: The role of microglial activation in traumatic brain injury (TBI) has been extensively described in established animal models. In contrast, very few studies have analysed this process in human patients, the majority being focused on the local reaction in the contused parenchyma. In this work, the main objective was the analysis of microglial activation in brain regions distant from the primary lesion. RESEARCH DESIGN: Morphological changes of microglia were evaluated in the cerebral cortex of patients deceased from TBI in comparison with control subjects...
2015: Brain Injury: [BI]
https://www.readbyqxmd.com/read/26022249/mapping-neuroinflammation-in-frontotemporal-dementia-with-molecular-pet-imaging
#16
REVIEW
Jing Zhang
Recent findings have led to a renewed interest and support for an active role of inflammation in neurodegenerative dementias and related neurologic disorders. Detection of neuroinflammation in vivo throughout the course of neurodegenerative diseases is of great clinical interest. Studies have shown that microglia activation (an indicator of neuroinflammation) may present at early stages of frontotemporal dementia (FTD), but the role of neuroinflammation in the pathogenesis of FTD is largely unknown. The first-generation translocator protein (TSPO) ligand ([(11)C]-PK11195) has been used to detect microglia activation in FTD, and the second-generation TSPO ligands have imaged neuroinflammation in vivo with improved pharmacokinetic properties...
May 29, 2015: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/25878273/in-vivo-pet-imaging-of-the-%C3%AE-4%C3%AE-2-nicotinic-acetylcholine-receptor-as-a-marker-for-brain-inflammation-after-cerebral-ischemia
#17
Abraham Martín, Boguslaw Szczupak, Vanessa Gómez-Vallejo, Maria Domercq, Ainhoa Cano, Daniel Padro, Clara Muñoz, Makoto Higuchi, Carlos Matute, Jordi Llop
PET imaging of nicotinic acetylcholine receptors (nAChRs) could become an effective tool for the diagnosis and therapy evaluation of neurologic diseases. Despite this, the role of nAChRs α4β2 receptors after brain diseases such as cerebral ischemia and its involvement in inflammatory reaction is still largely unknown. To investigate this, we performed in parallel in vivo magnetic resonance imaging (MRI) and positron emission tomography (PET) with 2[(18)F]-fluoro-A85380 and [(11)C]PK11195 at 1, 3, 7, 14, 21, and 28 d after middle cerebral artery occlusion (MCAO) in rats...
April 15, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/25722450/the-18-kda-mitochondrial-translocator-protein-in-human-gliomas-an-11c-r-pk11195-pet-imaging-and-neuropathology-study
#18
Zhangjie Su, Federico Roncaroli, Pascal F Durrenberger, David J Coope, Konstantina Karabatsou, Rainer Hinz, Gerard Thompson, Federico E Turkheimer, Karolina Janczar, Daniel Du Plessis, Andrew Brodbelt, Alan Jackson, Alexander Gerhard, Karl Herholz
UNLABELLED: The 18-kDa mitochondrial translocator protein (TSPO) is upregulated in high-grade astrocytomas and can be imaged by PET using the selective radiotracer (11)C-(R)PK11195. We investigated (11)C-(R)PK11195 binding in human gliomas and its relationship with TSPO expression in tumor tissue and glioma-associated microglia/macrophages (GAMs) within the tumors. METHODS: Twenty-two glioma patients underwent dynamic (11)C-(R)PK11195 PET scans and perfusion MR imaging acquisition...
April 2015: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/25701708/in-vivo-analysis-of-neuroinflammation-in-the-late-chronic-phase-after-experimental-stroke
#19
H L Walter, M Walberer, M A Rueger, H Backes, D Wiedermann, M Hoehn, B Neumaier, R Graf, G R Fink, M Schroeter
BACKGROUND AND PURPOSE: In vivo imaging of inflammatory processes is a valuable tool in stroke research. We here investigated the combination of two imaging modalities in the chronic phase after cerebral ischemia: magnetic resonance imaging (MRI) using intravenously applied ultra small supraparamagnetic iron oxide particles (USPIO), and positron emission tomography (PET) with the tracer [(11)C]PK11195. METHODS: Rats were subjected to permanent middle cerebral artery occlusion (pMCAO) by the macrosphere model and monitored by MRI and PET for 28 or 56 days, followed by immunohistochemical endpoint analysis...
April 30, 2015: Neuroscience
https://www.readbyqxmd.com/read/25537727/in-vivo-imaging-and-characterization-of-18-f-dpa-714-a-potential-new-tspo-ligand-in-mouse-brain-and-peripheral-tissues-using-small-animal-pet
#20
Caterina Vicidomini, Mariarosaria Panico, Adelaide Greco, Sara Gargiulo, Anna Rita Daniela Coda, Antonella Zannetti, Matteo Gramanzini, Giovanni N Roviello, Mario Quarantelli, Bruno Alfano, Bertrand Tavitian, Frederic Dollé, Marco Salvatore, Arturo Brunetti, Sabina Pappatà
INTRODUCTION: The translocator protein 18 kDa (TSPO), a biochemical marker of neuroinflammation, is highly expressed in the brain activated microglia and it is also expressed by peripheral inflammatory cells and normal peripheral tissues. Thus, development of radioligands for the TSPO may contribute to further understanding the in vivo TSPO function in central and peripheral inflammatory processes and other pathologies. Here, we report the biodistribution, the specific binding and the radiometabolites of [(18)F]DPA-714, a promising fluorinated PET radiotracer, in normal mice using a microPET/CT scanner...
March 2015: Nuclear Medicine and Biology
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