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Theranostics 2014; 4(6):592-603. doi:10.7150/thno.7757 This issue Cite

Research Paper

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

Thomas Bonnard^1,2, Gonord Yang¹, Anne Petiet³, Véronique Ollivier¹, Oualid Haddad⁴, Denis Arnaud¹, Liliane Louedec¹, Laure Bachelet-Violette¹, Sidi Mohammed Derkaoui¹, Didier Letourneur^1,2, Cedric Chauvierre¹, Catherine Le Visage^1✉

1. Inserm, U698, Cardiovascular Bio-Engineering, X. Bichat hospital, 46 Rue H. Huchard, F-75018, Paris, France;
2. Institut Galilée, Université Paris 13, Sorbonne Paris Cité, F-93430, Villetaneuse, France;
3. IFR 02, UFR de Médecine, site Bichat, Université Paris Diderot, F-75018, Paris, France;
4. UFR SMBH, Université Paris 13, Sorbonne Paris Cité, F-93000, Bobigny, France.

✉ Corresponding author: Email: catherine.levisagefr

Abstract

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.

Keywords: Fucoidan, P-Selectin, ^99mTc, Ligand, Radiolabeled.

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