{"id":1010,"date":"2020-05-05T12:22:48","date_gmt":"2020-05-05T10:22:48","guid":{"rendered":"http:\/\/www.biomaps.universite-paris-saclay.fr\/?page_id=1010"},"modified":"2020-05-19T14:41:00","modified_gmt":"2020-05-19T12:41:00","slug":"nouveaux-radiotraceurs-nouvelles-cibles","status":"publish","type":"page","link":"https:\/\/www.biomaps.universite-paris-saclay.fr\/index.php\/nouveaux-radiotraceurs-nouvelles-cibles\/","title":{"rendered":"Nouveaux radiotraceurs, nouvelles cibles"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-page\" data-elementor-id=\"1010\" class=\"elementor elementor-1010\" data-elementor-post-type=\"page\">\n\t\t\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-2152332 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"2152332\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-c404784\" data-id=\"c404784\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-0820ebd elementor-widget elementor-widget-text-editor\" data-id=\"0820ebd\" 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 class=\"has-medium-font-size\">Cet axe de recherche vise \u00e0 identifier, synth\u00e9tiser, radiomarquer et r\u00e9aliser les premi\u00e8res \u00e9tapes de caract\u00e9risation <em>in vitro<\/em> et <em>in vivo<\/em> de nouveaux agents d\u2019imagerie (petites mol\u00e9cules, peptides, anticorps\u2026) permettant d\u2019\u00e9tudier <em>in vivo<\/em> de nouvelles cibles pharmacologiques d\u2019int\u00e9r\u00eat en neurologie et en oncologie. L\u2019identification de nouvelles cibles pharmacologiques \u00e0 partir de donn\u00e9es de la litt\u00e9rature ou en \u00e9troite collaboration avec des cliniciens nous conduit \u00e0 rechercher de nouveaux pharmacophores (\u00e9tudes <em>in silico<\/em>, bibliographie\u2026). Une fois identifi\u00e9s, ces pharmacophores peuvent \u00eatre radiomarqu\u00e9s isotopiquement si leur structure chimique le permet (c\u2019est-\u00e0-dire par remplacement d\u2019un atome stable par son isotopologue radioactif), ou \u00eatre modifi\u00e9s, dans une approche de chimio-modulation orient\u00e9e, rendant ensuite le radiomarquage possible (Fig. 1.I).\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-6127455 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"6127455\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-2277569\" data-id=\"2277569\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-bfa4fff elementor-widget elementor-widget-image\" data-id=\"bfa4fff\" 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<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img fetchpriority=\"high\" decoding=\"async\" width=\"18196\" height=\"5825\" src=\"https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/Nouveaux-traceurs-fig-1_fran\u00e7ais.png\" class=\"attachment-full size-full wp-image-1083\" alt=\"\" srcset=\"https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/Nouveaux-traceurs-fig-1_fran\u00e7ais.png 18196w, https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/Nouveaux-traceurs-fig-1_fran\u00e7ais-150x48.png 150w, https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/Nouveaux-traceurs-fig-1_fran\u00e7ais-500x160.png 500w, https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/Nouveaux-traceurs-fig-1_fran\u00e7ais-768x246.png 768w, https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/Nouveaux-traceurs-fig-1_fran\u00e7ais-1536x492.png 1536w, https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/Nouveaux-traceurs-fig-1_fran\u00e7ais-2048x656.png 2048w\" sizes=\"(max-width: 18196px) 100vw, 18196px\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">Figure 1: I : Exemple de modulation d\u2019un pharmacophore ciblant les r\u00e9cepteurs cannabinoides de type 2 pour introduire un atome de fluor en vue d'un radiomarquage au fluor-18 [1] ; II : Exemples de r\u00e9f\u00e9rences froides, pr\u00e9curseurs et radiotraceurs marqu\u00e9s au fluor-18 et carbone-11 [1,2]<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-d3c40bb elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"d3c40bb\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-0cf398a\" data-id=\"0cf398a\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-151a6b9 elementor-widget elementor-widget-text-editor\" data-id=\"151a6b9\" 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 class=\"has-medium-font-size\">Ces diff\u00e9rentes \u00e9tapes impliquent la mise en \u0153uvre de m\u00e9thodes standard ou innovantes de synth\u00e8se organique pour d\u00e9finir et pr\u00e9parer \u00ab\u00a0le bin\u00f4me\u00a0\u00bb de mol\u00e9cules\u00a0: r\u00e9f\u00e9rence froide \/ pr\u00e9curseur, avant de proc\u00e9der au radiomarquage proprement dit avec un \u00e9metteur de positons \u00e0 vie br\u00e8ve (<sup>11<\/sup>C ou <sup>18<\/sup>F) (Fig. 1.II).\n\n<p class=\"has-medium-font-size\">Viennent ensuite les premi\u00e8res caract\u00e9risations <em>in vitro<\/em> (affinit\u00e9, s\u00e9lectivit\u00e9, autoradiographie, passage de la BHE, relations structure-activit\u00e9, pr\u00e9diction du m\u00e9tabolisme\u2026) permettant de s\u00e9lectionner les meilleurs candidats pour les \u00e9tudes pr\u00e9liminaires de biodistribution <em>in vivo<\/em>. Les m\u00e9thodes <em>in vitro<\/em> impliquent des \u00e9tudes de \u00ab\u00a0binding\u00a0\u00bb pour mesurer l\u2019affinit\u00e9 et la s\u00e9lectivit\u00e9 des nouveaux compos\u00e9s et des techniques d\u2019autoradiographie pour \u00e9valuer leur biodistribution et s\u00e9lectivit\u00e9 tissulaires (Fig. 2.I). L\u2019\u00e9valuation du m\u00e9tabolisme, <em>in vitro<\/em> et <em>in vivo<\/em> par des techniques HPLC et LC\/MS, de ces futurs agents d\u2019imagerie permet (i) de pr\u00e9dire la pr\u00e9sence de (radio)m\u00e9tabolites susceptibles d\u2019interagir avec la cible pharmacologique et entra\u00eener une confusion dans les images ou un biais dans la quantification du signal TEP, (ii) de synth\u00e9tiser des mol\u00e9cules plus stables <em>in vivo<\/em> (Fig. 2. II). Ces \u00e9tudes pr\u00e9cliniques contribuent \u00e0 optimiser le choix et la structure des candidats potentiels.\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-29f67de elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"29f67de\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-a860e43\" data-id=\"a860e43\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-4162118 elementor-widget elementor-widget-image\" data-id=\"4162118\" 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<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" width=\"1758\" height=\"837\" src=\"https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/Nouveaux-tracerus-Figure-2-fran\u00e7ais.jpg\" class=\"attachment-full size-full wp-image-1084\" alt=\"\" srcset=\"https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/Nouveaux-tracerus-Figure-2-fran\u00e7ais.jpg 1758w, https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/Nouveaux-tracerus-Figure-2-fran\u00e7ais-150x71.jpg 150w, https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/Nouveaux-tracerus-Figure-2-fran\u00e7ais-500x238.jpg 500w, https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/Nouveaux-tracerus-Figure-2-fran\u00e7ais-768x366.jpg 768w, https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/Nouveaux-tracerus-Figure-2-fran\u00e7ais-1536x731.jpg 1536w\" sizes=\"(max-width: 1758px) 100vw, 1758px\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">Figure 2: I. Autoradiograhie in vitro: Exemple de distribution du traceur [18F]12 et \u00e9valuation de sa s\u00e9lectivit\u00e9 par comp\u00e9tition dans un mod\u00e8le de surexpression de TSPO [3] ; II. M\u00e9tabolisme in vitro\/in vivo du DPA-714 [4]<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-7116a29 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"7116a29\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-0d57837\" data-id=\"0d57837\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-4b61d26 elementor-widget elementor-widget-text-editor\" data-id=\"4b61d26\" 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 class=\"has-medium-font-size\">Le(s) meilleur(s) candidats sont ensuite \u00e9valu\u00e9s <em>in vivo<\/em> tant pour leur biodistribution que leur m\u00e9tabolisme plasmatique et tissulaire afin de d\u00e9finir les premiers param\u00e8tres pharmacocin\u00e9tiques. Cette derni\u00e8re \u00e9tape est r\u00e9alis\u00e9e en \u00e9troite collaboration avec les \u00e9quipes de <strong>BioMaps<\/strong> sp\u00e9cialis\u00e9es en imagerie pr\u00e9clinique dans le domaine des maladies du SNC (Fig. 3) ou en oncologie.\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-8b50c19 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"8b50c19\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-f386e66\" data-id=\"f386e66\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-91c18bd elementor-widget elementor-widget-image\" data-id=\"91c18bd\" 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<figure class=\"wp-caption\">\n\t\t\t\t\t\t\t\t\t\t<img decoding=\"async\" width=\"2000\" height=\"593\" src=\"https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/nouveaux-traceurs-Figure-3-francais-et-anglais.png\" class=\"attachment-full size-full wp-image-1085\" alt=\"\" srcset=\"https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/nouveaux-traceurs-Figure-3-francais-et-anglais.png 2000w, https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/nouveaux-traceurs-Figure-3-francais-et-anglais-150x44.png 150w, https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/nouveaux-traceurs-Figure-3-francais-et-anglais-500x148.png 500w, https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/nouveaux-traceurs-Figure-3-francais-et-anglais-768x228.png 768w, https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/05\/nouveaux-traceurs-Figure-3-francais-et-anglais-1536x455.png 1536w\" sizes=\"(max-width: 2000px) 100vw, 2000px\" \/>\t\t\t\t\t\t\t\t\t\t\t<figcaption class=\"widget-image-caption wp-caption-text\">Figure 3: I: Biodistribution du compos\u00e9 [18F]2 ; II: Evaluation de la s\u00e9lectivit\u00e9 pour les r\u00e9cepteurs cannabinoides de type 2; III: Evaluation du m\u00e9tabolisme plasmatique par HPLC [1]<\/figcaption>\n\t\t\t\t\t\t\t\t\t\t<\/figure>\n\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-2894c14 elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"2894c14\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-11f0efd\" data-id=\"11f0efd\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-f1a9db9 elementor-widget elementor-widget-text-editor\" data-id=\"f1a9db9\" 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 class=\"has-medium-font-size\">Sont en cours d\u2019\u00e9tudes:\n<ul>\n \t<li><strong class=\"has-medium-font-size\"><em>Les radiotraceurs de la neuroinflammation (TSPO, CB2, P2Y12, CYP): <\/em><\/strong><\/li>\n<\/ul>\n<p class=\"has-medium-font-size\">De nombreux radiotraceurs ont \u00e9t\u00e9 \u00e9valu\u00e9s pour \u00e9tudier la <strong>TSPO<\/strong>, une prot\u00e9ine reconnue comme biomarqueur des processus de neuroinflammation (projet FP7 INMiND 2012-2017) associ\u00e9e \u00e0 des maladies du SNC. Le [<sup>18<\/sup>F]DPA-714, un ligand de la TSPO, a poursuivi son d\u00e9veloppement jusque chez l\u2019homme, dans plusieurs protocoles cliniques pour le diagnostic et le suivi th\u00e9rapeutique de maladies neurod\u00e9g\u00e9n\u00e9ratives [5,6]. Depuis, d\u2019autres cibles pharmacologiques ont \u00e9t\u00e9 explor\u00e9es, comme les r\u00e9cepteurs cannabino\u00efdes de type 2 (<strong>CB2R<\/strong>) avec le [<sup>18<\/sup>F]FC0324 [1]. Plus r\u00e9cemment, nous avons d\u00e9but\u00e9 la synth\u00e8se de nouveaux candidats pour \u00e9valuer le r\u00f4le des r\u00e9cepteurs <strong>P2Y12<\/strong> dans la neuroinflammation.\n\nDe par leur implication dans la neuroinflammation et les maladies neurod\u00e9g\u00e9n\u00e9ratives, les cytochromes P450 tels que <strong>CYP<\/strong>46A1, CYP27A1, CYP7B1 impliqu\u00e9s dans le m\u00e9tabolisme de st\u00e9ro\u00efdes et en particulier dans l\u2019hom\u00e9ostasie du cholest\u00e9rol c\u00e9r\u00e9bral constituent de nouvelles cibles pharmacologiques originales. Un de nos projets consiste \u00e0 identifier et caract\u00e9riser un ligand sp\u00e9cifique du CYP46A1, \u00e9tudier la distribution et l\u2019activit\u00e9 de cet enzyme c\u00e9r\u00e9bral dans des conditions normales et pathologiques. Enfin, le meilleur candidat sera radiomarqu\u00e9 avec le fluor-18 ou le carbone-11 et \u00e9valu\u00e9 dans les mod\u00e8les pr\u00e9cliniques de maladies du SNC.\n<ul>\n \t<li><strong class=\"has-medium-font-size\"><em>Les radiotraceurs en oncologie (prot\u00e9ines du cycle cellulaire) <\/em><\/strong><\/li>\n<\/ul>\n<p class=\"has-medium-font-size\">Nous avons d\u00e9but\u00e9 r\u00e9cemment un programme de d\u00e9veloppement de traceurs pour imager des prot\u00e9ines qui interviennent dans la r\u00e9gulation du cycle cellulaire (<strong>p53, AMPK, SK1<\/strong>). Des pharmacophores ont d\u2019ores et d\u00e9j\u00e0 \u00e9t\u00e9 identifi\u00e9s et des analogues qui pourront \u00eatre radiomarqu\u00e9s au fluor-18 sont en cours de d\u00e9veloppement. Une fois obtenus, ces compos\u00e9s seront caract\u00e9ris\u00e9s <em>in vitro,<\/em> puis les meilleurs candidats \u00e9valu\u00e9s <em>in vivo<\/em> dans des mod\u00e8les adapt\u00e9s. L\u2019imagerie <em>in vivo<\/em> de ces prot\u00e9ines, natives ou mut\u00e9es, pourra permettre de stratifier les patients en fonction des mutations et de mieux adapter les traitements.\n\nNous d\u00e9veloppons \u00e9galement le radiomarquage isotopique (sans modification de structure) de m\u00e9dicaments anti-canc\u00e9reux tels que le <strong>[<sup>11<\/sup>C]erlotinib<\/strong>, le <strong>[<sup>18<\/sup>F]binimetinib<\/strong> ou le <strong>[<sup>18<\/sup>F]crizotinib<\/strong>. L\u2019imagerie TEP de ces m\u00e9dicaments permettra d\u2019obtenir des donn\u00e9es pharmacocin\u00e9tiques et pharmacodynamiques compl\u00e9mentaires et de mieux d\u00e9crypter les voies de signalisation de ces m\u00e9dicaments et comprendre certains ph\u00e9nom\u00e8nes de r\u00e9sistance.\n\nEnfin, dans le domaine en forte expansion de l\u2019<strong>ImmunoTEP<\/strong> (imagerie TEP avec des anticorps ou fragments radiomarqu\u00e9s), nous avons impl\u00e9ment\u00e9 le radiomarquage d\u2019anticorps au zirconium-89 et nous d\u00e9veloppons aussi des approches originales de radiomarquages de fragments d\u2019anticorps avec du fluro-18 (voir <em>Nouvelles m\u00e9thodologies de radiomarquage<\/em>).\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-1bd88ff elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"1bd88ff\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-af87848\" data-id=\"af87848\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-6ffd11b elementor-widget elementor-widget-text-editor\" data-id=\"6ffd11b\" 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<h3>R\u00e9f\u00e9rences<\/h3><p>[1] Caill\u00e9 F, Cacheux F, Peyronneau MA, Jego B, Jaumain E, Pottier G, Ullmer C, Grether U, Winkeler A, Dolle F, Damont A, Kuhnast B. <strong>From Structure-Activity Relationships on Thiazole Derivatives to the <em>In Vivo<\/em> Evaluation of a New Radiotracer for Cannabinoid Subtype 2 PET Imaging<\/strong> (<strong>2017<\/strong>), <em>Mol Pharm<\/em>, 14, 4064-4078. <a href=\"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.molpharmaceut.7b00746\" target=\"_blank\" rel=\"noopener\">doi:10.1021\/acs.molpharmaceut.7b00746<\/a><\/p><p>[2] Goutal S, Gerstenmayer M, Auvity S,\u00a0Caill\u00e9 F, M\u00e9riaux S, Buvat I, Larrat B, Tournier N.\u00a0<strong>Physical blood-brain barrier disruption induced by focused ultrasound does not overcome the transporter-mediated efflux of erlotinib.<\/strong> (<strong>2018<\/strong>), <em>J Control Release<\/em>, 292, 210-220. ] <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/30415015\/?from_term=Caill%C3%A9+F&amp;from_pos=10\" target=\"_blank\" rel=\"noopener\">doi:10.1016\/j.jconrel.2018.11.009<\/a><\/p><p>[3] Damont A, M\u00e9dran-Navarrete V, Cacheux F, Kuhnast B, Pottier G, Bernards N, Marguet F, Puech F, Boisgard R, Doll\u00e9 F. <strong>Novel Pyrazolo[1,5-a]pyrimidines as Translocator Protein 18 kDa (TSPO) Ligands: Synthesis, in Vitro Biological Evaluation, [<sup>18<\/sup>F]-Labeling, and <em>in vivo<\/em> Neuroinflammation PET Images<\/strong>. (<strong>2015<\/strong>), <em>J Med Chem<\/em>, 58, 7449-7464. <a href=\"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jmedchem.5b00932\" target=\"_blank\" rel=\"noopener\">doi: 10.1021\/acs.jmedchem.5b00932<\/a><\/p><p>[4] Peyronneau MA, Saba W, Goutal S, Damont A, Doll\u00e9 F, Kassiou M, Bottlaender M, Valette H. <strong>Metabolism and quantification of [<sup>18<\/sup>F]DPA-714, a new TSPO positron emission tomography radioligand.<\/strong> (<strong>2013<\/strong>), <em>Drug Metab Dispos<\/em>, 41, 122-131. <a href=\"http:\/\/dmd.aspetjournals.org\/content\/early\/2012\/10\/12\/dmd.112.046342\" target=\"_blank\" rel=\"noopener\">doi:10.1124\/dmd.112.046342<\/a><\/p><p>[5] Hamelin L, Lagarde J, Doroth\u00e9e G, Leroy C, Labit M, Comley RA, de Souza LC, Corne H, Dauphinot L, Bertoux M, Dubois B, Gervais P, Colliot O, Potier MC, Bottlaender M, Sarazin M. <strong>Early and protective microglial activation in Alzheimer&rsquo;s disease: a prospective study using <sup>18<\/sup>F-DPA-714 PET imaging<\/strong>. (<strong>2016<\/strong>), <em>Brain<\/em>, 139, 1252-1264. <a href=\"https:\/\/academic.oup.com\/brain\/article\/139\/4\/1252\/2464345\" target=\"_blank\" rel=\"noopener\">doi:10.1093\/brain\/aww017<\/a><\/p><p>[6] Hamelin L, Lagarde J, Doroth\u00e9e G, Potier MC, Corlier F, Kuhnast B, Caill\u00e9 F, Dubois B, Fillon L, Chupin M, Bottlaender M, Sarazin M. <strong>Distinct dynamic profiles of microglial activation are associated with progression of Alzheimer&rsquo;s disease<\/strong>. (<strong>2018<\/strong>), <em>Brain<\/em>, 141, 1855-1870. <a href=\"https:\/\/academic.oup.com\/brain\/article\/141\/6\/1855\/4955843\" target=\"_blank\" rel=\"noopener\">doi:10.1093\/brain\/awy079.<\/a><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>Cet axe de recherche vise \u00e0 identifier, synth\u00e9tiser, radiomarquer et r\u00e9aliser les premi\u00e8res \u00e9tapes de caract\u00e9risation in vitro et in vivo de nouveaux agents d\u2019imagerie (petites mol\u00e9cules, peptides, anticorps\u2026) permettant d\u2019\u00e9tudier in vivo de nouvelles cibles pharmacologiques d\u2019int\u00e9r\u00eat en neurologie et en oncologie. L\u2019identification de nouvelles cibles pharmacologiques \u00e0 partir de donn\u00e9es de la litt\u00e9rature [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":615,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"guten_post_layout_featured_media_urls":{"full":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-e1609957375858.png",750,126,false],"thumbnail":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-100x100.png",100,100,true],"medium":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-150x25.png",150,25,true],"medium_large":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-768x129.png",640,108,true],"large":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-500x84.png",500,84,true],"1536x1536":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-1536x257.png",1536,257,true],"2048x2048":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-e1609957375858.png",750,126,false],"guten_post_layout_landscape_large":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-1200x318.png",1200,318,true],"guten_post_layout_portrait_large":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-1200x318.png",1200,318,true],"guten_post_layout_square_large":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-1200x318.png",1200,318,true],"guten_post_layout_landscape":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-600x318.png",600,318,true],"guten_post_layout_portrait":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-600x318.png",600,318,true],"guten_post_layout_square":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-600x318.png",600,318,true],"sciencex-single-team-thumb":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-360x270.png",360,270,true],"sciencex-team-thumbnail":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-263x216.png",263,216,true],"sciencex-event-thumbnail":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-555x318.png",555,318,true],"sciencex-event-gallery-thumb":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-227x168.png",227,168,true],"sciencex-blog-thumb":["https:\/\/www.biomaps.universite-paris-saclay.fr\/wp-content\/uploads\/2020\/04\/Footer-100x80.png",100,80,true]},"_links":{"self":[{"href":"https:\/\/www.biomaps.universite-paris-saclay.fr\/index.php\/wp-json\/wp\/v2\/pages\/1010"}],"collection":[{"href":"https:\/\/www.biomaps.universite-paris-saclay.fr\/index.php\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.biomaps.universite-paris-saclay.fr\/index.php\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.biomaps.universite-paris-saclay.fr\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.biomaps.universite-paris-saclay.fr\/index.php\/wp-json\/wp\/v2\/comments?post=1010"}],"version-history":[{"count":4,"href":"https:\/\/www.biomaps.universite-paris-saclay.fr\/index.php\/wp-json\/wp\/v2\/pages\/1010\/revisions"}],"predecessor-version":[{"id":1086,"href":"https:\/\/www.biomaps.universite-paris-saclay.fr\/index.php\/wp-json\/wp\/v2\/pages\/1010\/revisions\/1086"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.biomaps.universite-paris-saclay.fr\/index.php\/wp-json\/wp\/v2\/media\/615"}],"wp:attachment":[{"href":"https:\/\/www.biomaps.universite-paris-saclay.fr\/index.php\/wp-json\/wp\/v2\/media?parent=1010"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}