{"id":795,"date":"2023-12-15T16:10:53","date_gmt":"2023-12-15T16:10:53","guid":{"rendered":"http:\/\/192.168.10.216\/?page_id=795"},"modified":"2024-09-07T19:45:52","modified_gmt":"2024-09-07T18:45:52","slug":"enzymes-contraste-et-theranostic","status":"publish","type":"page","link":"https:\/\/www.rmsb.u-bordeaux.fr\/fr\/la-recherche\/equipe-imrt\/enzymes-contraste-et-theranostic\/","title":{"rendered":"Enzymes, contraste et th\u00e9ranostic"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-page\" data-elementor-id=\"795\" class=\"elementor elementor-795\">\n\t\t\t\t<div class=\"elementor-element elementor-element-351e065b e-flex e-con-boxed wpr-particle-no wpr-jarallax-no wpr-parallax-no wpr-sticky-section-no e-con e-parent\" data-id=\"351e065b\" data-element_type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-98c4761 elementor-widget elementor-widget-heading\" data-id=\"98c4761\" data-element_type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.21.0 - 26-05-2024 *\/\n.elementor-heading-title{padding:0;margin:0;line-height:1}.elementor-widget-heading .elementor-heading-title[class*=elementor-size-]>a{color:inherit;font-size:inherit;line-height:inherit}.elementor-widget-heading .elementor-heading-title.elementor-size-small{font-size:15px}.elementor-widget-heading .elementor-heading-title.elementor-size-medium{font-size:19px}.elementor-widget-heading .elementor-heading-title.elementor-size-large{font-size:29px}.elementor-widget-heading .elementor-heading-title.elementor-size-xl{font-size:39px}.elementor-widget-heading .elementor-heading-title.elementor-size-xxl{font-size:59px}<\/style><h1 class=\"elementor-heading-title elementor-size-default\">Enzymes, contraste et th\u00e9ranostic<\/h1>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-7c8e7d4 elementor-widget elementor-widget-text-editor\" data-id=\"7c8e7d4\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.21.0 - 26-05-2024 *\/\n.elementor-widget-text-editor.elementor-drop-cap-view-stacked .elementor-drop-cap{background-color:#69727d;color:#fff}.elementor-widget-text-editor.elementor-drop-cap-view-framed .elementor-drop-cap{color:#69727d;border:3px solid;background-color:transparent}.elementor-widget-text-editor:not(.elementor-drop-cap-view-default) .elementor-drop-cap{margin-top:8px}.elementor-widget-text-editor:not(.elementor-drop-cap-view-default) .elementor-drop-cap-letter{width:1em;height:1em}.elementor-widget-text-editor .elementor-drop-cap{float:left;text-align:center;line-height:1;font-size:50px}.elementor-widget-text-editor .elementor-drop-cap-letter{display:inline-block}<\/style>\t\t\t\t<!-- wp:paragraph -->\n<p>Axe dirig\u00e9 par Philippe Mellet<\/p>\n<!-- \/wp:paragraph -->\n\n<!-- wp:list -->\n<ul><!-- wp:list-item -->\n<li><strong>Agents de contraste et de th\u00e9ranostique sensibles aux activit\u00e9s enzymatiques \/ Enzyme activity-triggered contrast and theranostics agents.<\/strong><\/li>\n<!-- \/wp:list-item --><\/ul>\n<!-- \/wp:list -->\n\n<!-- wp:paragraph -->\n<p>L\u2019IRM anatomique est devenue incontournable par la pr\u00e9cision de ses images et son innocuit\u00e9. Cependant un besoin d\u2019imagerie mol\u00e9culaire produisant de nouveaux types de contraste appara\u00eet car dans de nombreuses pathologies les changements biochimiques se manifestent tr\u00e8s longtemps avant les modifications anatomiques d\u00e9tectables.<\/p>\n<!-- \/wp:paragraph -->\n\n<!-- wp:paragraph -->\n<p>Les activit\u00e9s enzymatiques sont des marqueurs tr\u00e8s pr\u00e9coces de nombreuses pathologies. Parmi ces enzymes les prot\u00e9ases sont particuli\u00e8rement int\u00e9ressantes. En effet dans les tissus sains l\u2019activit\u00e9 prot\u00e9olytique est tr\u00e8s strictement r\u00e9gul\u00e9e dans l\u2019espace et le temps et donc presque ind\u00e9tectable. Par contre dans certaines pathologies une activit\u00e9 forte, localis\u00e9e et surtout persistante s\u2019installe. Parmi ces pathologies nous nous int\u00e9resserons \u00e0 l\u2019inflammation, aux tumeurs solides et \u00e0 la pancr\u00e9atite aig\u00fce ou chronique.<\/p>\n<!-- \/wp:paragraph -->\n\n<!-- wp:paragraph -->\n<p><strong><em>Volet diagnostique&nbsp;:<\/em><\/strong>&nbsp;Nous continuerons \u00e0 d\u00e9velopper et am\u00e9liorer des agents de contraste pour les prot\u00e9ases pr\u00e9sentes dans les pathologies cit\u00e9es ci-dessus en liaison \u00e9troite avec les projets de polarisation dynamique (PDN) \u00e0 champ faible et ultra faible (axe \u00ab Innovations en IRM \u00e0 champ faible&nbsp;\u00bb). Nous modifierons les nitroxydes \u00e0 d\u00e9placement de raie pr\u00e9c\u00e9demment d\u00e9velopp\u00e9s dans le cadre des ANR NITROMRI et PULMOZYMAGE. En particulier l\u2019adaptation de ces substrats pour r\u00e9v\u00e9ler l\u2019activit\u00e9 des metallo-prot\u00e9ases sera un nouveau d\u00e9fi. De plus nous travaillerons sur la persistance et la biodistribution de ces agents de contraste dans les diff\u00e9rents compartiments cibles&nbsp;: poumons, pancr\u00e9as, tumeurs et cerveaux.<\/p>\n<!-- \/wp:paragraph -->\n\n<!-- wp:paragraph -->\n<p>Diff\u00e9rents principes physiques sont utilis\u00e9s pour provoquer un contraste en IRM rehauss\u00e9e par polarisation&nbsp; dynamique&nbsp;:<\/p>\n<!-- \/wp:paragraph -->\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-66c4978 e-flex e-con-boxed wpr-particle-no wpr-jarallax-no wpr-parallax-no wpr-sticky-section-no e-con e-parent\" data-id=\"66c4978\" data-element_type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-bf52f90 elementor-widget elementor-widget-image\" data-id=\"bf52f90\" data-element_type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.21.0 - 26-05-2024 *\/\n.elementor-widget-image{text-align:center}.elementor-widget-image a{display:inline-block}.elementor-widget-image a img[src$=\".svg\"]{width:48px}.elementor-widget-image img{vertical-align:middle;display:inline-block}<\/style>\t\t\t\t\t\t\t\t\t\t<img fetchpriority=\"high\" decoding=\"async\" width=\"1024\" height=\"495\" src=\"https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2023\/12\/capture-1024x495-1.jpg\" class=\"attachment-large size-large wp-image-799\" alt=\"\" srcset=\"https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2023\/12\/capture-1024x495-1.jpg 1024w, https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2023\/12\/capture-1024x495-1-300x145.jpg 300w, https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2023\/12\/capture-1024x495-1-768x371.jpg 768w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/>\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-b975946 e-flex e-con-boxed wpr-particle-no wpr-jarallax-no wpr-parallax-no wpr-sticky-section-no e-con e-parent\" data-id=\"b975946\" data-element_type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-b1c3a7d elementor-widget elementor-widget-text-editor\" data-id=\"b1c3a7d\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p>1.<strong>Rivot, A., N. Jugniot, S. Jacoutot, N. Vanthuyne, P. Massot, P. Mellet, S.R.A. Marque, G. Audran, et al.<\/strong>\u00a02021. Magnetic Resonance Imaging of Protease-Mediated Lung Tissue Inflammation and Injury. ACS omega\u00a0<em>6<\/em>:15012-15016.<\/p>\n<p>2.<strong>Parzy, E., D. Boudries, S. Jacoutot, M. Albalat, N. Vanthuyne, J.M. Franconi, P. Mellet, E. Thiaudiere, et al.<\/strong>\u00a02021. Enzymatic activity monitoring through dynamic nuclear polarization in Earth magnetic field. Journal of magnetic resonance\u00a0<em>333<\/em>:107095.<\/p>\n<p>3.<strong>Jugniot, N., P. Voisin, A. Bentaher, and P. Mellet.<\/strong>\u00a02019. Neutrophil Elastase Activity Imaging: Recent Approaches in the Design and Applications of Activity-Based Probes and Substrate-Based Probes. Contrast media &amp; molecular imaging\u00a0<em>2019<\/em>:7417192.<\/p>\n<p>4.<strong>Audran, G., S. Jacoutot, N. Jugniot, S.R.A. Marque, and P. Mellet.<\/strong>\u00a02019. Shifting-Nitroxides to Investigate Enzymatic Hydrolysis of Fatty Acids by Lipases Using Electron Paramagnetic Resonance in Turbid Media. Analytical chemistry\u00a0<em>91<\/em>:5504-5507.<\/p>\n<p>5.<strong>Jugniot, N., I. Duttagupta, A. Rivot, P. Massot, C. Cardiet, A. Pizzoccaro, M. Jean, N. Vanthuyne, et al.<\/strong>\u00a02018. An elastase activity reporter for Electronic Paramagnetic Resonance (EPR) and Overhauser-enhanced Magnetic Resonance Imaging (OMRI) as a line-shifting nitroxide. Free radical biology &amp; medicine\u00a0<em>126<\/em>:101-112.<\/p>\n<p>6.<strong>Duttagupta, I., N. Jugniot, G. Audran, J.M. Franconi, S.R.A. Marque, P. Massot, P. Mellet, E. Parzy, et al.<\/strong>\u00a02018. Selective On\/Off-Nitroxides as Radical Probes to Investigate Non-radical Enzymatic Activity by Electron Paramagnetic Resonance. Chemistry\u00a0<em>24<\/em>:7615-7619.<\/p>\n<p>7.<strong>Audran, G., L. Bosco, P. Bremond, J.M. Franconi, N. Koonjoo, S.R. Marque, P. Massot, P. Mellet, et al.<\/strong>\u00a02015. Enzymatically Shifting Nitroxides for EPR spectroscopy and Overhauser-Enhanced Magnetic Resonance Imaging. Angewandte Chemie.<\/p>\n<p>8.<strong>Koonjoo, N., E. Parzy, P. Massot, M. Lepetit-Coiffe, S.R.A. Marque, J.-M. Franconi, E. Thiaudiere, and P. Mellet.<\/strong>\u00a02014. In vivo Overhauser-enhanced MRI of proteolytic activity. Contrast media &amp; molecular imaging\u00a0<em>9<\/em>:363-371.<\/p>\n<p>9.<strong>Parzy, E., V. Bouchaud, P. Massot, P. Voisin, N. Koonjoo, D. Moncelet, J.-M. Franconi, E. Thiaudiere, and P. Mellet.<\/strong>\u00a02013. Overhauser-Enhanced MRI of Elastase Activity from In Vitro Human Neutrophil Degranulation. Plos One\u00a0<em>8<\/em>.<\/p>\n<p>10.<strong>Massot, P., E. Parzy, L. Pourtau, P. Mellet, G. Madelin, S. Marque, J.-M. Franconi, and E. Thiaudiere.<\/strong>\u00a02012. In vivo high-resolution 3D Overhauser-enhanced MRI in mice at 0.2?T. Contrast media &amp; molecular imaging\u00a0<em>7<\/em>:45-50.<\/p>\n<p>11.<strong>Mellet, P., P. Massot, G. Madelin, S.R.A. Marque, E. Harte, J.-M. Franconi, and E. Thiaudiere.<\/strong>\u00a02009. New Concepts in Molecular Imaging: Non-Invasive MRI Spotting of Proteolysis Using an Overhauser Effect Switch. Plos One\u00a0<em>4<\/em>.<\/p>\n<p><strong><em>Volet th\u00e9ranostique\u00a0:<\/em><\/strong>\u00a0Il existe un besoin pressant de trouver des chimioth\u00e9rapies pour le cancer qui ne soient pas toxiques pour les cellules en division (et en cons\u00e9quence pour le syst\u00e8me immunitaire et la lign\u00e9e h\u00e9matopo\u00ef\u00e9tique dans son ensemble) et qui ne suscitent pas de s\u00e9lection et donc des r\u00e9sistances aux traitements. Cette recherche s\u2019appuie sur la propri\u00e9t\u00e9 rare des alkoxyamines de se scinder spontan\u00e9ment en deux radicaux libre, l\u2019un \u00e9tant un nitroxyde stable qui peut \u00eatre vu en PDN l\u2019autre \u00e9tant un radical alkyl instable et, comme nous l\u2019avons montr\u00e9, cytotoxique. L\u2019ajout d\u2019un peptide substrat d\u2019une enzyme cible permets de stabiliser la mol\u00e9cule en pro-drogue activable par une prot\u00e9ase. Les probl\u00e8mes physico-chimiques et enzymologiques complexes afin d\u2019obtenir une pro-drogue infiniment stable, activable par les prot\u00e9ases et qui s\u2019homolyse rapidement apr\u00e8s activation ont \u00e9t\u00e9 r\u00e9solu dans le quinquennat pr\u00e9c\u00e9dent. L\u2019attaque radicalaire des cellules \u00e9tant al\u00e9atoire par nature les r\u00e9sistances ont peu de chance d\u2019appara\u00eetre. Le ciblage se faisant par la pr\u00e9sence de l\u2019activit\u00e9 prot\u00e9olytique pr\u00e9sente dans le microenvironnement des tumeurs les effets secondaires des antimitotiques ne doivent pas se produire. Nous ciblerons dans un premier temps les prot\u00e9ases \u00e0 serine des tumeurs (urokinase, PSA, Elastase) puis nous adapterons ces pro-drogues aux m\u00e9talloprot\u00e9ases (MMP-9, MMp-2, MMp-7\u2026.). In vivo l\u2019IRM sera utilis\u00e9e pour \u00e9valuer l\u2019efficacit\u00e9 des traitements en partenariat avec l\u2019axe \u00ab\u00a0IRM Quantitative Multi-Param\u00e9trique\u00a0\u00bb\u00a0 De plus le contraste PDN cr\u00e9\u00e9 par la lib\u00e9ration de nitroxyde par la drogue activ\u00e9e in situ sera le t\u00e9moin de la quantit\u00e9 du d\u00e9p\u00f4t de la drogue et indiquera le lieu de son d\u00e9p\u00f4t ouvrant ainsi la possibilit\u00e9 d\u2019un traitement personnalis\u00e9, ceci en partenariat avec l\u2019axe \u00ab\u00a0Innovations en IRM \u00e0 champ faible\u00a0\u00bb<\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-3291a62 e-flex e-con-boxed wpr-particle-no wpr-jarallax-no wpr-parallax-no wpr-sticky-section-no e-con e-parent\" data-id=\"3291a62\" data-element_type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-273384b elementor-widget elementor-widget-image\" data-id=\"273384b\" data-element_type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" width=\"293\" height=\"468\" src=\"https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2023\/12\/Sans-titre.png\" class=\"attachment-large size-large wp-image-803\" alt=\"\" srcset=\"https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2023\/12\/Sans-titre.png 293w, https:\/\/www.rmsb.u-bordeaux.fr\/wp-content\/uploads\/2023\/12\/Sans-titre-188x300.png 188w\" sizes=\"(max-width: 293px) 100vw, 293px\" \/>\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-adb61c8 e-flex e-con-boxed wpr-particle-no wpr-jarallax-no wpr-parallax-no wpr-sticky-section-no e-con e-parent\" data-id=\"adb61c8\" data-element_type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-dec15d4 elementor-widget elementor-widget-text-editor\" data-id=\"dec15d4\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p>Le m\u00eame raisonnement peut s\u2019appliquer aux bact\u00e9ries r\u00e9sistantes, un probl\u00e8me mondial de sant\u00e9 publique. En effet les bact\u00e9ries s\u00e9cr\u00e8tent des enzymes de r\u00e9sistance aux antibiotiques ou de virulence comme des prot\u00e9ases. Diff\u00e9rents programmes et collaborations en ce sens seront d\u00e9velopp\u00e9s durant ce nouveau quinquennat avec une extension vers la lutte contre le paludisme et les schistosomes.<\/p>\n<p><a id=\"post-1444-_ENREF_1\"><\/a>1.<strong>Seren, S., J.-P. Joly, P. Voisin, V. Bouchaud, G. Audran, S.R.A. Marque, and P. Mellet.<\/strong>\u00a02022. Neutrophil Elastase-Activatable Prodrugs Based on an Alkoxyamine Platform to Deliver Alkyl Radicals Cytotoxic to Tumor Cells. Journal of medicinal chemistry.<\/p>\n<p><a id=\"post-1444-_ENREF_2\"><\/a>2.<strong>Audran, G., S.R.A. Marque, and P. Mellet.<\/strong>\u00a02020. Smart Alkoxyamines: A New Tool for Smart Applications. Accounts of chemical research.<\/p>\n<p><a id=\"post-1444-_ENREF_3\"><\/a>3.<strong>Albalat, M., G. Audran, M. Holzritter, S.R.A. Marque, P. Mellet, N. Vanthuyne, and P. Voisin.<\/strong>\u00a02020. An enzymatic acetal\/hemiacetal conversion for the physiological temperature activation of the alkoxyamine C\u2013ON bond homolysis. Organic Chemistry Frontiers.<\/p>\n<p><a id=\"post-1444-_ENREF_4\"><\/a>4.<strong>Audran, G., L. Bosco, P. Br\u00e9mond, N. Jugniot, S.R.A. Marque, P. Massot, P. Mellet, T. Moussounda Moussounda Koumba, et al.<\/strong>\u00a02019. Enzymatic triggering of C\u2013ON bond homolysis of alkoxyamines. Organic Chemistry Frontiers.<\/p>\n<p><a id=\"post-1444-_ENREF_5\"><\/a>5.<strong>Moncelet, D., P. Voisin, N. Koonjoo, V. Bouchaud, P. Massot, E. Parzy, G. Audran, J.-M. Franconi, et al.<\/strong>\u00a02014. Alkoxyamines: Toward a New Family of Theranostic Agents against Cancer. Molecular Pharmaceutics\u00a0<em>11<\/em>:2412-2419.<\/p>\n<p><a id=\"post-1444-_ENREF_6\"><\/a>6.<strong>Audran, G., P. Bremond, J.-M. Franconi, S.R.A. Marque, P. Massot, P. Mellet, E. Parzy, and E. Thiaudiere.<\/strong>\u00a02014. Alkoxyamines: a new family of pro-drugs against cancer. Concept for theranostics. Organic &amp; biomolecular chemistry\u00a0<em>12<\/em>:719-723.<\/p>\n<p><strong>Personnes impliqu\u00e9es :<\/strong><\/p>\n<ul>\n<li>\n<p>Philippe Mellet (IR INSERM)<\/p>\n<p>ORCID\u00a0:\u00a0<a href=\"https:\/\/orcid.org\/0000-0001-5499-9735\">https:\/\/orcid.org\/0000-0001-5499-9735<\/a><\/p>\n<p>Researchgate:\u00a0<a href=\"https:\/\/www.researchgate.net\/profile\/Philippe-Mellet\">https:\/\/www.researchgate.net\/profile\/Philippe-Mellet<\/a><\/p>\n<\/li>\n<li>\n<p>Pierre Voisin (Pr Em\u00e9rite)<\/p>\n<\/li>\n<li>\n<p>Eric Thiaudi\u00e8re (Pr) <span style=\"font-size: 16px;\">ORCID : <\/span><a style=\"font-size: 16px; background-color: #ffffff;\" href=\"https:\/\/orcid.org\/0000-0002-9993-4035\">https:\/\/orcid.org\/0000-0002-9993-4035<\/a><\/p>\n<\/li>\n<li>\n<p>V\u00e9ronique Bouchaud (Technicienne)<\/p>\n<\/li>\n<\/ul>\n<p><strong>Financements\u00a0:<\/strong><\/p>\n<ul>\n<li>Europe FETOPEN PrimoGAIA<\/li>\n<li>Financement 80\/Prime MITI<\/li>\n<\/ul>\n<p><strong>Collaborations\u00a0:<\/strong><\/p>\n<ul>\n<li>Institut de chimie radicalaire (Marseille) \u00e9quipe CRAB. Prof. Sylvain Marque\u00a0; Prof. G\u00e9rard Audran<\/li>\n<li>CRC Paris 6\u00a0; Michel Arthur (DR INSERM)<\/li>\n<li>INSERM ERL 1289 Toulouse\u00a0; Fran\u00e7oise Benoit-Vical (DR INSERM)<\/li>\n<li>INSERM U 1100 (Tours)\u00a0; Brice Korkmaz (CR INSERM)<\/li>\n<li>UMR CNRS 5244 (Perpignan) Prof. J\u00e9rome Boissier<\/li>\n<li>Consortium \u00ab\u00a0Primoga\u00efa\u00a0\u00bb<\/li>\n<\/ul>\n<p><strong>Doctorants\/Post-doctorants\u00a0:<\/strong><\/p>\n<p>\u00a0<\/p>\n<p><strong>Anciens membres:<\/strong><\/p>\n<p>Seda Seren, Post-doctorante<\/p>\n<p>Natacha Jugniot, Doctorante<\/p>\n<p>Samantha Labarbe, Master 2 et Th\u00e8se de pharmacie<\/p>\n<p>Th\u00e9o Merc\u00e9, Master 1<\/p>\n<p>Damien Moncelet, Doctorant<\/p>\n<p>Neha Koonjoo, doctorante<\/p>\n<p><strong>Publications :<\/strong><\/p>\n<div>\n<p>P. Mellet :<a tabindex=\"-1\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=mellet+p&amp;sort=date\" target=\"_blank\" rel=\"external nofollow noopener noreferrer\">https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=mellet+p&amp;sort=date<\/a><\/p>\n<div>E. Thiaudi\u00e8re : <a tabindex=\"-1\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=thiaudi%C3%A8re+e&amp;sort=date\" target=\"_blank\" rel=\"external nofollow noopener noreferrer\">https:\/\/pubmed.ncbi.nlm.nih.gov\/?term=thiaudi\u00e8re+e&amp;sort=date<\/a><\/div>\n<div>\u00a0<\/div>\n<\/div>\n<div>\u00a0<\/div>\n<div>\u00a0<\/div>\n<div class=\"voirAussi\">\u00a0<\/div>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>Enzymes, contraste et th\u00e9ranostic Axe dirig\u00e9 par Philippe Mellet L\u2019IRM anatomique est devenue incontournable par la pr\u00e9cision de ses images et son innocuit\u00e9. Cependant un besoin d\u2019imagerie mol\u00e9culaire produisant de nouveaux types de contraste appara\u00eet car dans de nombreuses pathologies les changements biochimiques se manifestent tr\u00e8s longtemps avant les modifications anatomiques d\u00e9tectables. Les activit\u00e9s enzymatiques sont des marqueurs tr\u00e8s pr\u00e9coces de nombreuses pathologies. Parmi ces enzymes les prot\u00e9ases sont particuli\u00e8rement int\u00e9ressantes. En effet dans les tissus sains l\u2019activit\u00e9 prot\u00e9olytique est tr\u00e8s strictement r\u00e9gul\u00e9e dans l\u2019espace et le temps et donc presque ind\u00e9tectable. Par contre dans certaines pathologies une activit\u00e9 forte, localis\u00e9e et surtout persistante s\u2019installe. Parmi ces pathologies nous nous int\u00e9resserons \u00e0 l\u2019inflammation, aux tumeurs solides et \u00e0 la pancr\u00e9atite aig\u00fce ou chronique. Volet diagnostique&nbsp;:&nbsp;Nous continuerons \u00e0 d\u00e9velopper et am\u00e9liorer des agents de contraste pour les prot\u00e9ases pr\u00e9sentes dans les pathologies cit\u00e9es ci-dessus en liaison \u00e9troite avec les projets de polarisation dynamique (PDN) \u00e0 champ faible et ultra faible (axe \u00ab Innovations en IRM \u00e0 champ faible&nbsp;\u00bb). Nous modifierons les nitroxydes \u00e0 d\u00e9placement de raie pr\u00e9c\u00e9demment d\u00e9velopp\u00e9s dans le cadre des ANR NITROMRI et PULMOZYMAGE. En particulier l\u2019adaptation de ces substrats pour r\u00e9v\u00e9ler l\u2019activit\u00e9 des metallo-prot\u00e9ases sera un nouveau d\u00e9fi. De plus nous travaillerons sur la persistance et la biodistribution de ces agents de contraste dans les diff\u00e9rents compartiments cibles&nbsp;: poumons, pancr\u00e9as, tumeurs et cerveaux. Diff\u00e9rents principes physiques sont utilis\u00e9s pour provoquer un contraste en IRM rehauss\u00e9e par polarisation&nbsp; dynamique&nbsp;: 1.Rivot, A., N. Jugniot, S. Jacoutot, N. Vanthuyne, P. Massot, P. Mellet, S.R.A. Marque, G. Audran, et al.\u00a02021. Magnetic Resonance Imaging of Protease-Mediated Lung Tissue Inflammation and Injury. ACS omega\u00a06:15012-15016. 2.Parzy, E., D. Boudries, S. Jacoutot, M. Albalat, N. Vanthuyne, J.M. Franconi, P. Mellet, E. Thiaudiere, et al.\u00a02021. Enzymatic activity monitoring through dynamic nuclear polarization in Earth magnetic field. Journal of magnetic resonance\u00a0333:107095. 3.Jugniot, N., P. Voisin, A. Bentaher, and P. Mellet.\u00a02019. Neutrophil Elastase Activity Imaging: Recent Approaches in the Design and Applications of Activity-Based Probes and Substrate-Based Probes. Contrast media &amp; molecular imaging\u00a02019:7417192. 4.Audran, G., S. Jacoutot, N. Jugniot, S.R.A. Marque, and P. Mellet.\u00a02019. Shifting-Nitroxides to Investigate Enzymatic Hydrolysis of Fatty Acids by Lipases Using Electron Paramagnetic Resonance in Turbid Media. Analytical chemistry\u00a091:5504-5507. 5.Jugniot, N., I. Duttagupta, A. Rivot, P. Massot, C. Cardiet, A. Pizzoccaro, M. Jean, N. Vanthuyne, et al.\u00a02018. An elastase activity reporter for Electronic Paramagnetic Resonance (EPR) and Overhauser-enhanced Magnetic Resonance Imaging (OMRI) as a line-shifting nitroxide. Free radical biology &amp; medicine\u00a0126:101-112. 6.Duttagupta, I., N. Jugniot, G. Audran, J.M. Franconi, S.R.A. Marque, P. Massot, P. Mellet, E. Parzy, et al.\u00a02018. Selective On\/Off-Nitroxides as Radical Probes to Investigate Non-radical Enzymatic Activity by Electron Paramagnetic Resonance. Chemistry\u00a024:7615-7619. 7.Audran, G., L. Bosco, P. Bremond, J.M. Franconi, N. Koonjoo, S.R. Marque, P. Massot, P. Mellet, et al.\u00a02015. Enzymatically Shifting Nitroxides for EPR spectroscopy and Overhauser-Enhanced Magnetic Resonance Imaging. Angewandte Chemie. 8.Koonjoo, N., E. Parzy, P. Massot, M. Lepetit-Coiffe, S.R.A. Marque, J.-M. Franconi, E. Thiaudiere, and P. Mellet.\u00a02014. In vivo Overhauser-enhanced MRI of proteolytic activity. Contrast media &amp; molecular imaging\u00a09:363-371. 9.Parzy, E., V. Bouchaud, P. Massot, P. Voisin, N. Koonjoo, D. Moncelet, J.-M. Franconi, E. Thiaudiere, and P. Mellet.\u00a02013. Overhauser-Enhanced MRI of Elastase Activity from In Vitro Human Neutrophil Degranulation. Plos One\u00a08. 10.Massot, P., E. Parzy, L. Pourtau, P. Mellet, G. Madelin, S. Marque, J.-M. Franconi, and E. Thiaudiere.\u00a02012. In vivo high-resolution 3D Overhauser-enhanced MRI in mice at 0.2?T. Contrast media &amp; molecular imaging\u00a07:45-50. 11.Mellet, P., P. Massot, G. Madelin, S.R.A. Marque, E. Harte, J.-M. Franconi, and E. Thiaudiere.\u00a02009. New Concepts in Molecular Imaging: Non-Invasive MRI Spotting of Proteolysis Using an Overhauser Effect Switch. Plos One\u00a04. Volet th\u00e9ranostique\u00a0:\u00a0Il existe un besoin pressant de trouver des chimioth\u00e9rapies pour le cancer qui ne soient pas toxiques pour les cellules en division (et en cons\u00e9quence pour le syst\u00e8me immunitaire et la lign\u00e9e h\u00e9matopo\u00ef\u00e9tique dans son ensemble) et qui ne suscitent pas de s\u00e9lection et donc des r\u00e9sistances aux traitements. Cette recherche s\u2019appuie sur la propri\u00e9t\u00e9 rare des alkoxyamines de se scinder spontan\u00e9ment en deux radicaux libre, l\u2019un \u00e9tant un nitroxyde stable qui peut \u00eatre vu en PDN l\u2019autre \u00e9tant un radical alkyl instable et, comme nous l\u2019avons montr\u00e9, cytotoxique. L\u2019ajout d\u2019un peptide substrat d\u2019une enzyme cible permets de stabiliser la mol\u00e9cule en pro-drogue activable par une prot\u00e9ase. Les probl\u00e8mes physico-chimiques et enzymologiques complexes afin d\u2019obtenir une pro-drogue infiniment stable, activable par les prot\u00e9ases et qui s\u2019homolyse rapidement apr\u00e8s activation ont \u00e9t\u00e9 r\u00e9solu dans le quinquennat pr\u00e9c\u00e9dent. L\u2019attaque radicalaire des cellules \u00e9tant al\u00e9atoire par nature les r\u00e9sistances ont peu de chance d\u2019appara\u00eetre. Le ciblage se faisant par la pr\u00e9sence de l\u2019activit\u00e9 prot\u00e9olytique pr\u00e9sente dans le microenvironnement des tumeurs les effets secondaires des antimitotiques ne doivent pas se produire. Nous ciblerons dans un premier temps les prot\u00e9ases \u00e0 serine des tumeurs (urokinase, PSA, Elastase) puis nous adapterons ces pro-drogues aux m\u00e9talloprot\u00e9ases (MMP-9, MMp-2, MMp-7\u2026.). In vivo l\u2019IRM sera utilis\u00e9e pour \u00e9valuer l\u2019efficacit\u00e9 des traitements en partenariat avec l\u2019axe \u00ab\u00a0IRM Quantitative Multi-Param\u00e9trique\u00a0\u00bb\u00a0 De plus le contraste PDN cr\u00e9\u00e9 par la lib\u00e9ration de nitroxyde par la drogue activ\u00e9e in situ sera le t\u00e9moin de la quantit\u00e9 du d\u00e9p\u00f4t de la drogue et indiquera le lieu de son d\u00e9p\u00f4t ouvrant ainsi la possibilit\u00e9 d\u2019un traitement personnalis\u00e9, ceci en partenariat avec l\u2019axe \u00ab\u00a0Innovations en IRM \u00e0 champ faible\u00a0\u00bb Le m\u00eame raisonnement peut s\u2019appliquer aux bact\u00e9ries r\u00e9sistantes, un probl\u00e8me mondial de sant\u00e9 publique. En effet les bact\u00e9ries s\u00e9cr\u00e8tent des enzymes de r\u00e9sistance aux antibiotiques ou de virulence comme des prot\u00e9ases. Diff\u00e9rents programmes et collaborations en ce sens seront d\u00e9velopp\u00e9s durant ce nouveau quinquennat avec une extension vers la lutte contre le paludisme et les schistosomes. 1.Seren, S., J.-P. Joly, P. Voisin, V. Bouchaud, G. Audran, S.R.A. Marque, and P. Mellet.\u00a02022. Neutrophil Elastase-Activatable Prodrugs Based on an Alkoxyamine Platform to Deliver Alkyl Radicals Cytotoxic to Tumor Cells. Journal of medicinal chemistry. 2.Audran, G., S.R.A. Marque, and P. Mellet.\u00a02020. Smart Alkoxyamines: A New Tool for Smart Applications. Accounts of chemical research. 3.Albalat, M., G. Audran, M. Holzritter, S.R.A. Marque, P. Mellet, N. Vanthuyne, and P. Voisin.\u00a02020. An enzymatic acetal\/hemiacetal conversion for the &hellip;<\/p>\n<p class=\"read-more\"> <a class=\"\" href=\"https:\/\/www.rmsb.u-bordeaux.fr\/fr\/la-recherche\/equipe-imrt\/enzymes-contraste-et-theranostic\/\"> <span class=\"screen-reader-text\">Enzymes, contraste et th\u00e9ranostic<\/span> Lire la suite\u00a0\u00bb<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"parent":507,"menu_order":1,"comment_status":"closed","ping_status":"closed","template":"","meta":{"site-sidebar-layout":"right-sidebar","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"_links":{"self":[{"href":"https:\/\/www.rmsb.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/pages\/795"}],"collection":[{"href":"https:\/\/www.rmsb.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.rmsb.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.rmsb.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.rmsb.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/comments?post=795"}],"version-history":[{"count":29,"href":"https:\/\/www.rmsb.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/pages\/795\/revisions"}],"predecessor-version":[{"id":1994,"href":"https:\/\/www.rmsb.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/pages\/795\/revisions\/1994"}],"up":[{"embeddable":true,"href":"https:\/\/www.rmsb.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/pages\/507"}],"wp:attachment":[{"href":"https:\/\/www.rmsb.u-bordeaux.fr\/fr\/wp-json\/wp\/v2\/media?parent=795"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}