Cargando…
Abdominal Aortic Aneurysms Targeted by Functionalized Polysaccharide Microparticles: a new Tool for SPECT Imaging
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) produc...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982130/ https://www.ncbi.nlm.nih.gov/pubmed/24723981 http://dx.doi.org/10.7150/thno.7757 |
_version_ | 1782311143473152000 |
---|---|
author | Bonnard, Thomas Yang, Gonord Petiet, Anne Ollivier, Véronique Haddad, Oualid Arnaud, Denis Louedec, Liliane Bachelet-Violette, Laure Derkaoui, Sidi Mohammed Letourneur, Didier Chauvierre, Cedric Le Visage, Catherine |
author_facet | Bonnard, Thomas Yang, Gonord Petiet, Anne Ollivier, Véronique Haddad, Oualid Arnaud, Denis Louedec, Liliane Bachelet-Violette, Laure Derkaoui, Sidi Mohammed Letourneur, Didier Chauvierre, Cedric Le Visage, Catherine |
author_sort | Bonnard, Thomas |
collection | PubMed |
description | 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 ((99m)Tc) 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 (99m)Tc 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. |
format | Online Article Text |
id | pubmed-3982130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-39821302014-04-10 Abdominal Aortic Aneurysms Targeted by Functionalized Polysaccharide Microparticles: a new Tool for SPECT Imaging Bonnard, Thomas Yang, Gonord Petiet, Anne Ollivier, Véronique Haddad, Oualid Arnaud, Denis Louedec, Liliane Bachelet-Violette, Laure Derkaoui, Sidi Mohammed Letourneur, Didier Chauvierre, Cedric Le Visage, Catherine Theranostics Research Paper 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 ((99m)Tc) 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 (99m)Tc 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. Ivyspring International Publisher 2014-03-11 /pmc/articles/PMC3982130/ /pubmed/24723981 http://dx.doi.org/10.7150/thno.7757 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. |
spellingShingle | Research Paper Bonnard, Thomas Yang, Gonord Petiet, Anne Ollivier, Véronique Haddad, Oualid Arnaud, Denis Louedec, Liliane Bachelet-Violette, Laure Derkaoui, Sidi Mohammed Letourneur, Didier Chauvierre, Cedric Le Visage, Catherine Abdominal Aortic Aneurysms Targeted by Functionalized Polysaccharide Microparticles: a new Tool for SPECT Imaging |
title | Abdominal Aortic Aneurysms Targeted by Functionalized Polysaccharide Microparticles: a new Tool for SPECT Imaging |
title_full | Abdominal Aortic Aneurysms Targeted by Functionalized Polysaccharide Microparticles: a new Tool for SPECT Imaging |
title_fullStr | Abdominal Aortic Aneurysms Targeted by Functionalized Polysaccharide Microparticles: a new Tool for SPECT Imaging |
title_full_unstemmed | Abdominal Aortic Aneurysms Targeted by Functionalized Polysaccharide Microparticles: a new Tool for SPECT Imaging |
title_short | Abdominal Aortic Aneurysms Targeted by Functionalized Polysaccharide Microparticles: a new Tool for SPECT Imaging |
title_sort | abdominal aortic aneurysms targeted by functionalized polysaccharide microparticles: a new tool for spect imaging |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982130/ https://www.ncbi.nlm.nih.gov/pubmed/24723981 http://dx.doi.org/10.7150/thno.7757 |
work_keys_str_mv | AT bonnardthomas abdominalaorticaneurysmstargetedbyfunctionalizedpolysaccharidemicroparticlesanewtoolforspectimaging AT yanggonord abdominalaorticaneurysmstargetedbyfunctionalizedpolysaccharidemicroparticlesanewtoolforspectimaging AT petietanne abdominalaorticaneurysmstargetedbyfunctionalizedpolysaccharidemicroparticlesanewtoolforspectimaging AT ollivierveronique abdominalaorticaneurysmstargetedbyfunctionalizedpolysaccharidemicroparticlesanewtoolforspectimaging AT haddadoualid abdominalaorticaneurysmstargetedbyfunctionalizedpolysaccharidemicroparticlesanewtoolforspectimaging AT arnauddenis abdominalaorticaneurysmstargetedbyfunctionalizedpolysaccharidemicroparticlesanewtoolforspectimaging AT louedecliliane abdominalaorticaneurysmstargetedbyfunctionalizedpolysaccharidemicroparticlesanewtoolforspectimaging AT bacheletviolettelaure abdominalaorticaneurysmstargetedbyfunctionalizedpolysaccharidemicroparticlesanewtoolforspectimaging AT derkaouisidimohammed abdominalaorticaneurysmstargetedbyfunctionalizedpolysaccharidemicroparticlesanewtoolforspectimaging AT letourneurdidier abdominalaorticaneurysmstargetedbyfunctionalizedpolysaccharidemicroparticlesanewtoolforspectimaging AT chauvierrecedric abdominalaorticaneurysmstargetedbyfunctionalizedpolysaccharidemicroparticlesanewtoolforspectimaging AT levisagecatherine abdominalaorticaneurysmstargetedbyfunctionalizedpolysaccharidemicroparticlesanewtoolforspectimaging |