A5083141148- Radiopharmaceutical Chemistry and Applications
- Medical Imaging Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Mass Spectrometry Techniques and Applications
- Cancer therapeutics and mechanisms
- S100 Proteins and Annexins
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Drug Transport and Resistance Mechanisms
- Fluorine in Organic Chemistry
- Chemical Synthesis and Analysis
- Glioma Diagnosis and Treatment
- Advanced Chemical Sensor Technologies
- Analytical Chemistry and Chromatography
- Adenosine and Purinergic Signaling
- Click Chemistry and Applications
- Biochemical and Molecular Research
- Cancer, Hypoxia, and Metabolism
- Toxin Mechanisms and Immunotoxins
- Immune Response and Inflammation
- Isotope Analysis in Ecology
- Advanced NMR Techniques and Applications
- Epilepsy research and treatment
- Alzheimer's disease research and treatments
- Pharmacological Effects and Toxicity Studies
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2014-2024
CEA Paris-Saclay
2015-2024
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
2020-2024
Université Paris-Saclay
2016-2024
Technologies pour la Santé
2015-2024
Institut de Biologie et Technologies
2015-2022
Institut d'Imagerie Biomédicale
2009-2021
Unité de Technologies Chimiques et Biologiques pour la Santé
2021
Metabo (Switzerland)
2019
Institut National de la Recherche Agronomique du Niger
2019
Large-scale suspect and non-targeted screening approaches based on high-resolution mass spectrometry (HRMS) are today available for chemical profiling holistic characterisation of biological samples. These advanced techniques allow the simultaneous detection a large number features, including markers human exposure. Such interest biomonitoring, environmental health studies support to risk assessment. Furthermore, these have promising capability detect chemicals emerging concern (CECs),...
Overexpression of the translocator protein, TSPO (18 kDa), formerly known as peripheral benzodiazepine receptor, is a hallmark activation cells monocytic lineage (microglia and macrophages) during neuroinflammation. Radiolabeling ligands enables detection neuroinflammatory lesions by PET. Two new radioligands, <sup>11</sup>C-labeled <i>N,N</i>-diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-α]pyrimidin-3-yl]acetamide (DPA-713) <sup>18</sup>F-labeled...
Focal cerebral ischemia leads to an inflammatory reaction involving overexpression of the peripheral benzodiazepine receptor (PBR)/18-kDa translocator protein (TSPO) in monocytic lineage (microglia and monocyte) astrocytes. Imaging PBR/TSPO by positron emission tomography (PET) using radiolabeled ligands can document processes induced ischemia. We performed vivo PET imaging with [(18)F]DPA-714 determine time course expression over several days after induction rats. In showed significant...
Neuroinflammation is a process characterised by drastic changes in microglial morphology and marked upregulation of the 18-kDa translocator protein (TSPO) on mitochondria. The continual increase incidence neuroinflammation neurodegenerative diseases poses major health issue many countries, requiring more innovative diagnostic monitoring tools. TSPO expression may constitute biomarker for brain inflammation that could be monitored using tracers as neuroimaging agents. From medical imaging...
Abstract Background High resolution mass spectrometry (HRMS) is being used increasingly in the context of suspect and non-targeted screening for identification bioorganic molecules. There correspondingly increasing awareness that higher confidence will require a systematic, group effort to increase fraction compounds with tandem spectra available central, publicly resources. While typical efforts only result tentative annotations moderate level confidence, library spectral matches yield or...
Constant improvements to the Orbitrap mass analyzer, such as acquisition speed, resolution, dynamic range and sensitivity have strengthened its value for large-scale identification quantification of metabolites in complex biological matrices. Here, we report development optimization Data Dependent Acquisition (DDA) Sequential Window all THeoretical fragment ions (SWATH-type) Independent (DIA) workflows on a high-field FusionTM TribridTM instrument robust human plasma. By using set 47...
Abstract Recently, a novel series of 2‐phenylpyrazolo[1,5‐ ]pyrimidineacetamides has been reported as selective ligands the translocator protein (18 kDa). Within this series, DPA‐714 ( N,N ‐diethyl‐2‐(2‐(4‐(2‐fluoroethoxy)phenyl)‐5,7‐dimethylpyrazolo[1,5‐ ]pyrimidin‐3‐yl)acetamide, K i =7.0 nM) is compound, which had designed with fluorine atom in its structure, allowing labelling fluorine‐18 (half‐life: 109.8 min) and vivo imaging using positron emission tomography. tosyloxy derivative...
[<sup>18</sup>F]DPA-714 [<i>N,N</i>-diethyl-2-(2-(4-(2[<sup>18</sup>F]-fluoroethoxy)phenyl)5,7dimethylpyrazolo[1,5a]pyrimidin-3-yl)acetamide] is a new radioligand currently used for imaging the 18-kDa translocator protein in animal models of neuroinflammation and recently humans. The biodistribution by positron emission tomography (PET) baboons vitro vivo metabolism were investigated rats, baboons, Whole-body PET experiments showed high uptake radioactivity kidneys, heart, liver,...
Microglia are potential targets for therapeutic intervention in neurological and neurodegenerative diseases affecting the central nervous system. In order to assess efficacy of therapies aimed reduce tissue damaging activities microglia and/or promote protective these cells, suitable pre-clinical clinical tools vivo analysis dynamics required. The aim this work was identify new translational markers anti-inflammatory / state development novel PET tracers. Methods: New...
Identification is a major challenge in metabolomics due to the large structural diversity of metabolites. Tandem mass spectrometry reference technology for studying fragmentation molecules and characterizing their structure. Recent instruments can fragment amounts compounds single acquisition. The search similarities within collection MS/MS spectra powerful approach facilitate identification new We propose an innovative de novo strategy searching exact patterns collections spectra. This...
A series of novel pyrazolo[1,5-a]pyrimidines, closely related to N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide (2, DPA-714), were synthesized and biologically in vitro evaluated for their potential bind the translocator protein 18 kDa (TSPO), a today recognized as an early biomarker neuroinflammatory processes. This is composed fluoroalkyl- fluoroalkynyl- analogues, prepared from common iodinated intermediate via Sonogashira coupling...
Epigenetic regulation of gene expression is tightly controlled by the dynamic modification histones chemical groups, diversity which has largely expanded over past decade with discovery lysine acylations, catalyzed from acyl-coenzymes A. We investigated dynamics acetylation and crotonylation on H3 H4 during mouse spermatogenesis. Lysine appeared to be significant abundance compared acetylation, particularly Lys27 histone (H3K27cr) that accumulates in sperm a cleaved form H3. identified...
Many neurological conditions result in the overexpression of translocator protein 18 kDa (TSPO), today recognized as a biomarker for microglial activation and neuroinflammation imaging. The pyrazolo[1,5-a]pyrimidine acetamides are particularly attractive class TSPO-specific ligands, prompting development several positron emission tomography (PET) radiotracers. This includes F-DPA, recently reported fluorinated ligand (K i = 1.7 nM), wherein fluorine atom is directly linked to phenyl moiety...
Neuroinflammation is associated with several neurological disorders, including Alzheimer's disease (AD). The translocator protein 18 kDa (TSPO), due to its overexpression during microglial activation and relatively low levels in the brain under normal neurophysiological conditions, commonly used as an vivo biomarker for neuroinflammation. Reported here preclinical evaluation of [18F]F-DPA, a promising new TSPO-specific radioligand, tool detection activated microglia at different ages...
Upregulation of the cannabinoid type 2 receptors (CB2R) unveils inflammation processes pathological disorders, such as cancer, pain, or neurodegenerative diseases. Among others, CB2R agonist A-836339 has been labeled with carbon-11 for PET imaging and displayed promising results in a mouse model Alzheimer's disease. The aim present work was to develop fluorinated analogs labeling fluorine-18 design new tracer imaging. Seven were synthesized two three steps their binding affinities...
Abstract Introduction Accuracy of feature annotation and metabolite identification in biological samples is a key element metabolomics research. However, the process often hampered by lack spectral reference data experimental conditions, as well logistical difficulties management exchange annotations between laboratories. Objectives To design an open-source infrastructure allowing hosting both nuclear magnetic resonance (NMR) mass spectra (MS), with ergonomic Web interface services to...
Abstract Nowadays, high‐resolution mass spectrometry is widely used for metabolomic studies. Thanks to its high sensitivity, it enables the detection of a large range metabolites. In metabolomics, continuous quest metabolite identification as complete and accurate possible has led during last decade an ever increasing development public MS databases (including LC‐MS data) concomitantly with bioinformatic tool expansion. To facilitate annotation process profiles obtained from biological...