In vivo targeted molecular imaging for activated platelets by mri using USPIO-fucoidan in rat abdominal aortic aneuryms model

POSTER PRESENTATIONInternational audienc

Synthèse, caractérisation et évaluation in vitro et in vivo d'agents de contraste pour l'imagerie moléculaire du coeur lipidique de la plaque d'athérosclérose

L objectif de mon projet de thèse est de développer des agents de contraste pour l imagerie par résonnance magnétique ciblant le cœur lipidique dans la plaque d athérosclérose. Imager et quantifier le cœur lipidique est un enjeu clinique majeur pour la détermination de la vulnérabilité de la plaque et donc l évaluation des risques de rupture. La stratégie retenue consiste à mimer le comportement des lipoprotéines, en particulier l apolipoprotéine A1 et son mimétique le D-4F qui se lie aux lipides par l intermédiaire d un cluster d acides aminés aromatiques. La première partie de mon travail a consisté à valider cette stratégie en utilisant une structure micellaire couplée à de la tyrosine-O-méthylester comme plateforme d imagerie du cœur lipidique. Cette approche a été validée chez l animal dans un modèle de souris ApoE-/- sous régime hypercholestérolémique développant des plaques d athérome. Dans la seconde partie de mon travail, nous avons utilisé un contrastophore paramagnétique construit sur une plateforme polysaccharidique versatile et aisément modifiable chimiquement. Plusieurs ligands ont été greffés sur cette plateforme: la tyrosine-O-méthylester, la trityrosine et le L-4F, énantiomère du D-4F. Les interactions des lipoprotéines, HDL et LDL, avec ces dérivés ont été mesurées par résonance plasmonique de surface, puis les produits ont été injectés chez la souris ApoE-/-. In vitro, le L-4F a présenté les interactions les plus fortes avec les lipoprotéines. In vivo, la prise de contraste du cœur lipidique avec le produit substitué par le L-4F s est révélée équivalente à celle du produit substitué par la trityrosine. Nous avons donc démontré la possibilité de réaliser une imagerie moléculaire du cœur lipidique de la plaque d athérosclérose à l aide d agents de contraste capables de mimer les interactions entre les lipoprotéines et les lipides.Imaging and quantifying the lipid core is a key to evaluate the risk of rupture of the atherosclerotic plaque. My goal is to develop MR contrast agent that will target the lipid core inside the atherosclerotic plaque. Our hypothesis is to mimic apolipoprotein A1 and mimetic D-4F behavior with lipids. D-4F is a soluble alpha helix peptide that binds to lipids via a cluster of aromatic amino acids. We believe that using a single aromatic amino acid or a combination of aromatic amino acids on a MR platform will efficiently target the lipid core. First, we developed a micellar platform functionalized with tyrosin-O-methylester. This compound was successfully tested in an ApoE-/- mouse model under western diet that develops atherosclerotic plaque. Then, we generalized this approach with a polysaccharide based MR contrast agent. Tyrosine-O-methylester was coupled to this platform as well as trityrosine and L-4F peptide. These compounds were evaluated first by surface plasmon resonance (SPR) on immobilized lipoproteins and then in the ApoE-/- mouse model. In vivo results indicate an enhancement in the atherosclerotic plaque and in the lipid core that validates our hypothesis.PARIS13-BU Sciences (930792102) / SudocSudocFranceF

Extruded starch as novel shape-memory bioresorbable biomedical device

International audienc

Synthesis and evaluation of a tri-tyrosine decorated dextran MR contrast agent for vulnerable plaque detection

International audienc

Shape-memory starch for resorbable biomedical devices

International audienceShape-memory resorbable materials were obtained by extrusion-cooking of potato starch with 20% glycerol under usual conditions. They presented an efficient shape-memory with a high recovery ratio (Rr > 90%).Their recovery could be triggered at 37 C in water. After water immersion at 37 C, the modulus decreased from 1 GPa to 2.4 MPa and remained almost constant over 21 days. Gamma-ray sterilization did not have a dramatic impact on their mechanical properties, despite a large decrease of molecular mass analyzed by asymmetrical flow field-flow fractionation coupled with multi-angle laser light scattering (AFFFF-MALLS). Samples implanted in a rat model exhibited normal tissue integration with a low inflammatory response. Thus, as previously investigated in the case of shape-memory synthetic polymers, natural starch, without chemical grafting, can now be considered for manufacturing innovative biodegradable devices for less-invasive surgery. (C) 2013 Elsevier Ltd. All rights reserved

Gadolinium/terbium hybrid macromolecular complexes for bimodal imaging of atherothrombosis

International audienc

Tyrosine polyethylene glycol (PEG)-micelle magnetic resonance contrast agent for the detection of lipid rich areas in atherosclerotic plaque

Vulnerable or high-risk atherosclerotic plaques often exhibit large lipid cores and thin fibrous caps that can lead to deadly vascular events when they rupture. In this study, polyethylene glycol (PEG)-micelles that incorporate a gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) amphiphile were used as an MR contrast agent. In an approach inspired by lipoproteins, the micelles were functionalized with tyrosine residues, an aromatic, lipophilic amino acid, to reach the lipid-rich areas of atherosclerotic plaque in a highly efficient manner. These micelles were applied to apolipoprotein E(-/-) (ApoE(-/-)) mice as a model of atherosclerosis. The abdominal aortas of the animals were imaged using T(1)-weighted (T(1)W) high-resolution MRI at 9.4T before and up to 48 h after the administration of the micelles. PEG-micelles modified with 15% tyrosine residues yielded a significant enhancement of the abdominal aortic wall at 6 and 24 h postinjection (pi) as compared to unmodified micelles. Fluorescence microscopy on histological sections of the abdominal aorta showed a correlation between lipid-rich areas and the distribution of the functionalized contrast agent in plaque. Using a simple approach, we demonstrated that lipid-rich areas in atherosclerotic plaque of ApoE(-/-) mice can be detected by MRI using Gd-DTPA micelle

Ultrasmall superparamagnetic iron oxide nanoparticles coated with fucoidan for molecular MRI of intraluminal thrombus

International audienc