Direct Comparison of [18F]F-DPA with [18F]DPA-714 and [11C]PBR28 for Neuroinflammation Imaging in the same Alzheimer’s Disease Model Mice and Healthy Controls

PurposeIn this study we compared the recently developed TSPO tracer [18F]F-DPA, with [18F]DPA-714 and [11C]PBR28 by performing in vivo PET imaging on the same Alzheimer’s disease mouse model APP/PS1-21 (TG) and wild-type (WT) mice with all three radiotracers.ProceduresTo compare the radiotracer uptake, percentage of injected dose/mL (%ID/mL), standardized uptake value ratios to cerebellum (SUVRCB), and voxel-wise analyses were performed.ResultsThe peak uptake of [18F]F-DPA was higher than 4.3% ID/mL, while [18F]DPA-714 reached just over 3% ID/mL, and [11C]PBR28 was over 4% ID/mL in only one brain region in the WT mice. The peak/60-min uptake ratios of [18F]F-DPA were significantly higher (p 18F]DPA-714 and [11C]PBR28. The differences in [18F]F-DPA SUVRCB between WT and TG mice were highly significant (p 18F]DPA-714 uptake was significantly higher in TG mice starting in the 20–40-min timeframe and increased thereafter, whereas [11C]PBR28 uptake became significant at 10–20 min (p Conclusions[18F]F-DPA displays higher brain uptake, higher TG-to-WT SUVRCB ratios, and faster clearance than [18F]DPA-714 and [11C]PBR28, and could prove useful for detecting low levels of inflammation and allow for shorter dynamic PET scans.</p

Identification of new molecular targets for PET imaging of the microglial anti-inflammatory activation state

Microglia are potential targets for therapeutic intervention in neurological and neurodegenerative diseases affecting the central nervous system. In order to assess the efficacy of therapies aimed to reduce the tissue damaging activities of microglia and/or to promote the protective potential of these cells, suitable pre-clinical and clinical tools for the in vivo analysis of microglia activities and dynamics are required. The aim of this work was to identify new translational markers of the anti-inflammatory/protective state of microglia for the development of novel PET tracers.Methods: New translational markers of the anti-inflammatory/protective activation state of microglia were selected by bioinformatic approaches and were in vitro and ex vivo validated by qPCR and immunohistochemistry in rodent and human samples. Once a viable marker was identified, a novel PET tracer was developed. This tracer was subsequently confirmed by autoradiography experiments in murine and human brain tissues.Results: Here we provide evidence that P2RYI2 expression increases in murine and human microglia following exposure to anti-inflammatory stimuli, and that its expression is modulated in the reparative phase of experimental and clinical stroke. We then synthesized a novel carbon-II labeled tracer targeting P2RYI2, showing increased binding in brain sections of mice treated with IL4, and low binding to brain sections of a murine stroke model and of a stroke patient.Conclusion: This study provides new translational targets for PET tracers for the anti-inflammatory/protective activation state of microglia and shows the potential of a rationale-based approach. It therefore paves the way for the development of novel non-invasive methodologies aimed to monitor the success of therapeutic approaches in various neurological diseases.</div

Synthèse et étude d'analogues de 2'-C-méthyl-ß-D-ribonucléosides à visée anti-hépatite C

MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Avidin/Biotin Bioinspired Platform for Dual In Vivo 18 F-PET/NIRF Molecular Imaging

International audienc

Hydrogen/deuterium exchange mass spectrometry in the world of small molecules

International audienceThe combined use of hydrogen/deuterium exchange (HDX) and massspectrometry (MS), referred to as HDX‐MS, is a powerful tool for exploringmolecular edifices and has been used for over 60 years. Initially for structuraland mechanistic investigation of low‐molecular weight organic compounds,then to study protein structure and dynamics, then, the craze to study smallmolecules by HDX‐MS accelerated and has not stopped yet. The purpose ofthis review is to present its different facets with particular emphasis onrecent developments and applications. Reversible H/D exchanges of mobi-lizable protons as well as stable exchanges of non‐labile hydrogen are con-sidered whether they are taking place in solution or in the gas phase, orenzymatically in a biological media. Some fundamental principles arerestated, especially for gas‐phase processes, and an overview of recentapplications, ranging from identification to quantification through the studyof metabolic pathways, is given

Synthesis and in vitro characterization of novel fluorinated derivatives of the translocator protein 18 kDa ligand CfO-DPA-714

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Combining chemical knowledge and quantum calculation for interpreting low-energy product ion spectra of metabolite adduct ions: Sodiated diterpene diester species as a case study

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Experimental Evidence That Electrospray-Produced Sodiated Lysophosphatidyl Ester Structures Exist Essentially as Protonated Salts

Sodiated lysoglycerophosphatidylethanolamine (LGPE) and lysoglycerophosphatidylcholine (LGPC) species dissociate under low collision energy by covalent bond cleavage resulting in product ions with either sodium retention or without sodium retention. For explaining these fragmentations, sodium chelation by heteroatoms (as charge-solvated structures) is often considered, and consequently, under keV collision conditions, sodium is "spectator" of cleavages (charge remote fragmentation). However, cleavage of such charge-solvated forms under low-energy conditions should result in sodium desolvation rather than covalent bond cleavage. In the present study, protonated salts are proposed as the main representative structures of the sodiated LGPE and LGPC forms. These structures are generated from sodiation of zwitterionic and betaine forms of LGPE and LGPC molecules, respectively. Experimental evidence to determine which structure is involved in the dissociations is provided, especially by comparing the dissociation of LGPL sodiated forms with that of sodiated polyethylene glycols. Energy-resolved mass spectrometry breakdown experiments were performed on a quadrupole time-of-flight instrument to demonstrate that both LGPE and LGPC sodiated forms exist as protonated salt structures. From such structures, proton migration by prototropy can result in different bond cleavages whereas the salt moiety remains spectator of these processes