Abdominal Aortic Aneurysms Targeted by Functionalized Polysaccharide Microparticles: a new Tool for SPECT Imaging

Autor: Thomas Bonnard, Sidi Mohammed Derkaoui, Laure Bachelet-Violette, Yang G, Cédric Chauvierre, Liliane Louedec, Le Visage C, Didier Letourneur, Anne Petiet, Ollivier, Arnaud D, Oualid Haddad
Přispěvatelé: Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), UFR de Médecine [Site Bichat] (IFR02), Université Paris Diderot - Paris 7 (UPD7)
Rok vydání: 2014
Předmět:
Blood Platelets
Male
medicine.medical_specialty
Pathology
P-selectin
Medicine (miscellaneous)
Ligand
[SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine
030204 cardiovascular system & hematology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Polysaccharides
In vivo
Fucoidan
Spect imaging
medicine
Animals
Humans
cardiovascular diseases
Platelet activation
[SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics
Rats
Wistar
Thrombus
Pharmacology
Toxicology and Pharmaceutics (miscellaneous)
ComputingMilieux_MISCELLANEOUS
Aorta
99mTc
030304 developmental biology
Tomography
Emission-Computed
Single-Photon
0303 health sciences
Chemistry
Technetium
medicine.disease
Microspheres
Rats
3. Good health
P-Selectin
Radiolabeled
cardiovascular system
Radiology
Radiopharmaceuticals
Molecular imaging
Technetium-99m
Aortic Aneurysm
Abdominal
Research Paper
Zdroj: Theranostics
Theranostics, Ivyspring International Publisher, 2014, 4 (6), pp.592-603. ⟨10.7150/thno.7757⟩
ISSN: 1838-7640
DOI: 10.7150/thno.7757
Popis: Aneurysm diagnostic is nowadays limited by the lack of technology that enables early detection and rupture risk prediction. New non invasive tools for molecular imaging are still required. In the present study, we present an innovative SPECT diagnostic tool for abdominal aortic aneurysm (AAA) produced from injectable polysaccharide microparticles radiolabeled with technetium 99m (99mTc) and functionalized with fucoidan, a sulfated polysaccharide with the ability to target P-Selectin. P-Selectin is a cell adhesion molecule expressed on activated endothelial cells and platelets which can be found in the thrombus of aneurysms, as well as in other vascular pathologies. Microparticles with a maximum hydrodynamic diameter of 4 µm were obtained by crosslinking the polysaccharides dextran and pullulan. They were functionalized with fucoidan. In vitro interactions with human activated platelets were assessed by flow cytometry that demonstrated a specific affinity of fucoidan functionalized microparticles for P-Selectin expressed by activated platelets. For in vivo AAA imaging, microparticles were radiolabeled with 99mTc and intravenously injected into healthy and AAA rats obtained by elastase perfusion through the aorta wall. Animals were scanned by SPECT imaging. A strong contrast enhancement located in the abdominal aorta of AAA rats was obtained, while no signal was obtained in healthy rats or in AAA rats after injection of non-functionalized control microparticles. Histological studies revealed that functionalized radiolabeled polysaccharide microparticles were localized in the AAA wall, in the same location where P-Selectin was expressed. These microparticles therefore constitute a promising SPECT imaging tool for AAA and potentially for other vascular diseases characterized by P-Selectin expression. Future work will focus on validating the efficiency of the microparticles to diagnose these other pathologies and the different stages of AAA. Incorporation of a therapeutic molecule is also considered.
Databáze: OpenAIRE
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