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Статті в журналах з теми "Sondes pour l’imagerie bimodale":
Jullien, Ludovic, and Arnaud Gautier. "Des sondes fluorescentes hybrides pour l’imagerie « à la demande » des protéines cellulaires." médecine/sciences 33, no. 6–7 (June 2017): 576–78. http://dx.doi.org/10.1051/medsci/20173306006.
Дисертації з теми "Sondes pour l’imagerie bimodale":
Fredy, Jean Wilfried. "Polyrotaxanes de cyclodextrines pour l’imagerie bimodale." Paris 6, 2013. http://www.theses.fr/2013PA066746.
In this thesis, we have designed a bimodal imaging agent (which combines two complementary techniques) based on a cyclodextrins (CD) polyrotaxane. Thus, functionalized CD bearing MRI contrast agent or fluorescent probes were threaded onto a polymer axis. This supramolecular approach provides a modular, flexible, biocompatible and biodegradable system. At first, several mono- or di-functionalized CDs have been synthesized selectively using CuAAC between a gadolinium complex (DOTA-Gd) or a fluorescent probe (BODIPY, cyanine, europium complex) and a CD with one or two azide functions. Then, thermodynamic and kinetic threading studies with different monomer units have shown the strong affinity of functionalized CDs for axes such as diaminododecane. However, PEG-like axis resulted to be poor guests for the CD. Model [3]rotaxanes with CDGd and CDGd2 were synthesized and have demonstrated a significant improvement of the relaxivity properties. Finally, polyrotaxanes based on functionalized CDs and a polyammonium axis have been successfully obtained. Their relaxivity properties were clearly improved compared to commercially available DOTA-Gd complex. Moreover, the fluorescence properties of the probes were preserved in the supramolecular architecture. These polyrotaxanes can now be considered for in vitro and in vivo biological studies
Boulay, Alexandre. "Sondes hétérobimétalliques pour l'imagerie bimodale." Toulouse 3, 2013. http://thesesups.ups-tlse.fr/2553/.
The multimodality approach in biomedical imaging has gained in popularity over the last decade with the development of a new class of contrast agents : the bimodal probes. The combination of complementary imaging modalities appears as a convenient pathway to overcome the weakness of each imaging modality and should allow access to microscopic and macroscopic data at the same time. The synthesis of new heterobimetallic complexes and the evaluation of their physico-chemical properties (aqueous stabilities, photophysical and relaxometric evaluations) are reported in this document. Using a bichelating ligand with a 2,2'-bipyridine moiety for the complexation of transition metal ions and a heptadentate moiety (2,6-bis[N,N-bis(carboxymethyl)aminomethyl] pyridine, PMN) for the chelation of lanthanide ions, various complexes were synthesized. Their physico-chemical properties were analyzed and they were founded sustainable with bimodal applications, especially in view of a promising MRI/Optical imaging duality application. The preliminary data of cytotoxicity and cellular microscopy studies are compatible with these conclusions. A second approach was used to built heterobimetallic tricarbonyl Re(I)-based complexes using the "2+1" complexation principle to introduce an auxiliary ligand in the coordination sphere of the metallic ion. According to this way, the first dinuclear Re(I)/99mTc(I) complex for an optical imaging/TEMP imaging was reported as well as an original structure combining Re(I) and Gd(III) ions for a MRI/Optical imaging duality application. The bioconjugation studies of this last compound are undergoing following favorable preliminary cytotoxicity experiments
Lescure, Robin. "Développement d’azaBODIPYs fonctionnalisables pour la conception de sondes d’imagerie bimodale et d’agents théranostiques." Thesis, Bourgogne Franche-Comté, 2020. https://nuxeo.u-bourgogne.fr/nuxeo/site/esupversions/21e2771a-9c75-46d7-9377-50e8f2536c32.
The in vivo use of optical imaging is still limited by the lack of near infrared emitting probes. This thesis work focuses on the optimization and valorization of a water-soluble fluorescent platform whose optical properties enable an in vivo use. Two distinct applications were investigated for this WazaBY (Water-soluble azaBODIPY) platform: use as a PET (or SPECT) / optical bimodal probe, and as a theranostic agent. Concerning the first project, we were able to develop a targetted SPECT/optical bimodal probe, which was radiometallated with indium 111. Using xenografted murine models, we were able to show a clear accumulation of the probe in the tumor 24 hours after injection. Moreover, the probe was validated as a contrast agent for fluorescence guided surgery experiment. The second project of this thesis began by the synthesis of a first generation of gold based theranostic agents. The goal was to develop a new therapeutic complex, which can be tracked in vitro and in vivo thanks to optical imaging. In vitro preliminary results showed that the theranostics displayed a cytotoxicity comparable to auranofin on the tested cell lines (4T1, MDA MB 231, CT26 and SW480). A second part of this project focused on the develoment of « smart » probes for a theranostic use. Those probes are designed to undergo photophysical properties changes, when their metallic centre, responsible for the therapeutic role, is released. Two molecules were synthesized, both displaying an on/off behavior
Galiyeva, Perizat. "Doped Ag-In-Zn-S and Ag-In-Ga-Zn-S QDs : synthesis and potential as dual-modality probes for magnetic resonance and fluorescence imaging of cells." Electronic Thesis or Diss., Université de Lorraine, 2021. http://www.theses.fr/2021LORR0118.
Since fluorescence imaging (FI) and magnetic resonance imaging (MRI) are among the most effective diagnostic tools, QDs with fluorescent and magnetic properties are of great interest as dual-modal probes. In this work, undoped and doped Ag-In-Zn-S (AIZS) and Ag-In-Ga-Zn-S (AIGZS) QDs were synthesized and investigated as bimodal probes for FI and MRI. Highly fluorescent AIZS QDs were prepared in organic media using DDT and OAm as capping ligands. Mn:AIZS QDs showed paramagnetic and superparamagnetic properties. AIZS and Mn:AIZS QDs were also transferred into aqueous phase using the amphiphilic PMAO polymer. Further, Mn, Gd or Fe-doped AIZS QDs were prepared in aqueous media, showed low cytotoxicity toward KB cells, and demonstrated potential as fluorescent probes for FI. Finally, AIGZS and Mn:AIGZS QDs, synthesized via a novel single precursor thermal decomposition method, showed high fluorescence and paramagnetic/superparamagnetic properties. Mn-doped aqueous transferred AIGZS QDs increased contrast in both T1-weighted and T2-weighted images with increasing in Mn loading
Ariztia, Julen. "Dérivés C-glycosidiques pour l’imagerie bimodale TEP/FPIR. Applications au marquage de dérivés peptidiques RGD." Electronic Thesis or Diss., Université de Lorraine, 2021. http://www.theses.fr/2021LORR0097.
The work developed in this thesis deals with C-glycosyl compounds for which new synthetic methodologies and applications in PET/NIRF imaging have been developed. Some peptides have a major role in the therapy and diagnostic of diverse pathologies and their conjugation with a fluorophore and a radioelement allow precise diagnostic and potential theranostic applications by surgery. The goal was to develop the synthesis of (radio)fluorinated and fluorescent dual probes for bimodal PET/NIRF imaging. An elaborated synthetic strategy was required to introduce a fluorine atom and a cyanine-type fluorophore, both being the specific probes of PET and NIRF imaging. Two main strategies were developed for the synthesis of these tools: the functionalization of C-glycosyl derivative including a [3.3.0]furofuranone scaffold and the functionalization of polyhydroxylated C-glycosyl compound. The protection/deprotection synthetic strategies have made possible the setting up of these various elements followed by the conjugation of two peptidic RGD derivatives by CuAAC “Click” reaction. The affinity of the two fluorinated and fluorescent derivatives for the integrins was in the same range (40 nM) than the RGD peptide alone, highlighting the benefit of the divalence of the agent. The radiofluorination of a dual PET/NIRF probe have been successfully achieved, allowing application for in vivo PET and NIRF imaging as well as NIRF-guided surgery
Gatin-Fraudet, Blaise. "Synthèse et évaluation de nouvelles sondes pour l’imagerie cellulaire du peroxyde d’hydrogène." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASF023.
Reactive oxygen species (ROS: hydrogen peroxide, hydroxyl and superoxide radicals) are by-products of aerobic metabolism. Among them, hydrogen peroxide (H2O2) plays a crucial role in a wide range of physiological processes in human. However, when our cells are subjected to oxidative stress conditions, its overproduction is directly or indirectly responsible for numerous damages at the molecular level, which can affect cellular mechanisms. The development of selective and sensitive tools allowing H2O2 detection in a biological context represents a great challenge for a better understanding of H2O2-mediated signalling in physiological and pathological processesTo date, several “off-on” small fluorescent probes triggered by H2O2 have been developed for its detection. Among them, probes based on the boronate oxidation are amongst the most effective for the detection of H2O2 in cellula. But these probes also suffer from lack of reactivity, which is not fully satisfactory for biological applications.The aim of this thesis project was to improve the reactivity of the trigger toward H2O2. To address this issue, the use of borinic acids as new trigger was envisioned. A new fluorogenic probe based on coumarin scaffold was synthetized and studied by 1H RMN, and by in vitro and in cellula fluorescence spectroscopy. In the second part of the project, the regioselectivity of the reaction was improved and new fluorogenic probes with or not an immolative spacer were studied
Mathieu, Paul. "Conception d’un agent de contraste nanostructuré pour l’imagerie médicale." Thesis, Toulouse 3, 2020. http://www.theses.fr/2020TOU30083.
During the 90’s, iron oxide nanoparticles (NPs) were considered as good Magnetic Resonance Imaging (MRI) contrast agents (CA). However, in 2010, the production of these NPs was stopped for economic reasons : their production was not profitable enough for the pharmaceutical laboratories. Taking into account the developpement of personnalized medicine, and a growing exigency in the field of diagnostics, the objective of this PhD., grounded on a collaboration between researchers in chemistry and sociology, is to question the relevance of NPs in the arising field of multimodal imaging. In this perspective, have been evaluated, as much the practicability of the synthesis as the interest of the medical field towards multimodal imaging CA. This collaboration takes place between one laboratory of sociology, the Centre d’Etude et de Recherche Travail Organisation Pouvoir, and two chemistry laboratories, the Laboratoire de Chimie de Coordination and the Laboratoire Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique. The collaboration with sociologists allowed us to better understand the challenges of the innovation process of a CA including, in the case of a « nano » CA, the aspect of « risks ». The investigations realized in the medical field provided : (a) a historical approach, to seize the reasons of the underutilization of iron oxide during the early 2000’s, leading to the withdrawal of these products and (b) an oversight of the properties deemed essential by the medical professionals, for a competitive CA. The state of the art of the three most used medical imaging techniques (MRI, Nuclear, and CT-Scan) as well as the developemement of the CA used for these techniques are herein reported. The synthesis of an iron/iron oxide, core/shell nanosystem coated with silica (NPFe@FeOx@SiO2) and its PEGylation are detailed. A complete study of its magnetic properties, and its stability in solution are presented. Lastly, the evaluation of these NPs as a CA for T2 MRI, and cytotoxicity assays on sain and cancerous cells are detailed. The results, corroborates their efficiency in imaging, as well as the absence of toxicity, particularly when the system is PEGylated. Then, this manuscript describes the first assays to obtain a multimodal CA. In a first part, we describe the synthesis of bismuth complexes and the attempts of their incorporation inside the silica shell, in order to create a multimodal CA in MRI and CT-Scan. Then the grafting of a gadolinium complex on the surface of the NPFe@FeOx@SiO2 and NPSiO2 have been carried out and the evaluation of its T1/T2 MRI and cytotoxicity properties are presented. In a last part, the locks towards the developpement of a bimodal CA will be discussed, and faced to the procurement locks of multimodal machines by hospitals in France. Indeed, if the developpement of these multimodal CA in the laboratory is in its golden age, the acquisition of multimodal equipement is uncertain, as the sociology study on the acquisitions and integration processes of PET-MRI in French hospitals has clearly shown. We then conclude on the benefits of the collaboration between chemists and sociologists and on the possibilities and perspectives opened by this work
François, Alison. "Élaboration de complexes hétérobinucléaires par approche chimie Click pour une application en imagerie bimodale." Toulouse 3, 2014. http://thesesups.ups-tlse.fr/2295/.
Biomedical imaging has been successfully developed during the last century, with efficient technics as MRI, nuclear or optical imaging. Constant improvements lead to "multimodality", i. E. Combining different imaging modalities to add strengths and limit weaknesses of each one. Following this new philosophy, multimodal contrast agents have been developed. We aimed to prepare new bimodal ones: we synthesized new heterobimetallic complexes thanks to Click chemistry reactions, and evaluated their properties as bimodal probes. The first structure is an optimization of our previous work: a Re(I)-pyridine-triazole (Re-pyta) is bound to an iminodiacetate, which chelates radioactive 99mTc(I). This heterobimetallic complex has shown good photophysical properties and an excellent stability in biological media. This results and the first biological studies, cytotoxicity and cellular uptake, are compatible with a potential application as a fluorescent/nuclear probes. After a bioconjugation of this compound, in vivo studies should be the next step of the validation of such a probe. The second structure type contains a DO3A pattern linked to a pyta moiety or a tetrazole equivalent, pytz, to resp. Chelate a Ln(III) ion and a Re(I) ion. Pyta and pytz moieties are used as Ln-sensitizers. We synthesized Ln monometallic complexes (Ln = Eu, Tb): they revealed excellent photophysical properties. Then, through the complexation of a second ion, Re(I), we showed it is possible to get the wanted heterobinuclear complexes
Christine, Thifanie. "Synthèses et propriétés de nouvelles structures à base de BODIPY pour l’imagerie bimodale TEP/IO et la génération d’oxygène singulet." Thesis, Bordeaux, 2020. http://www.theses.fr/2020BORD0239.
Medical imaging is a very important tool for the diagnosis of numerous diseases. The positron emission tomography (PET scan) is one of the most employed technique for its high sensibility, but the very short lifetime of the radionuclide used implies a very fast synthesis of the radioactive tracer.1,2 Optical imaging (OI) avoids the use of radioactive elements, but its limited sensibility in deep tissues can hamper its in vivo application. In order to obtain more modular probes depending on the need of the biologist (in vitro or in vivo studies), the development of new bimodal tracers is becoming an important research axis. In this context, new bimodal BODIPY-based molecules (fluorescent) that could be labelled by 11C (PET) have been synthesized. The different structures were conjugated to oestradiol to target the tumour cells of breast cancer. In vivo studies are being carried out to evaluate the biodistribution of the [13C]-labelled molecules. In parallel, their modification in photosensitizers for the production of singlet oxygen has also been considered for potential applications in the field of photodynamic therapy. On the other hand, several BODIPY-based photosensitizers have been synthesized and evaluated in a photooxygenation reaction, and their application to other types of reaction are in progress
Médran-Navarrete, Vincent. "Synthèse de nouvelles sondes moléculaires marquées au fluor-18 pour l’imagerie de la neuroinflammation par Tomographie par Emission de Positons." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA112097/document.
The work presented in this manuscript aims to describe the synthesis of new ligands of the translocation protein 18 kDa (TSPO), their in vitro evaluation and, for the most promising candidates, their isotopic radiolabelling with the short-lived positron emitter fluorine-18 (t1/2 : 109.8 minutes). The ultimate goal of this work consists in developing new molecular probes, or biomarkers, for imaging neuroinflammation in a non-invasive and atraumatic manor using Positron Emission Tomography (PET). Neuroinflammatory processes have been identified in Alzheimer and Parkinson diseases, MS and various psychiatric pathologies.The radioligand of choice for imaging TSPO is currently [18F]DPA-714, a pyrazolo[1,5-a]pyrimidine radiolabelled with fluorine-18 which has been recently prepared in our laboratories. However, [18F]DPA-714 undergoes a rapid in vivo loss of the radioactive fluorine by cleavage of the fluoroalkoxy chain as demonstrated in metabolic studies. Therefore, my PhD project aimed to design and develop new structurally related analogues of DPA-714 where the linkage between the main backbone and the fluorine-18 would be reinforced. To this extent, nineteen compounds were prepared and their affinity towards the TSPO was evaluated. Two promising candidates, coded DPA-C5yne and CfO-DPA-714, were radiolabelled with fluorine-18 with good radiochemical yields (20-30 %) and high specific radioactivities (50-90 GBq/µmol). These radioligands were also evaluated by PET imaging at the preclinical stage and displayed equivalent or slightly improved results when compared to [18F]DPA-714