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) 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.
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;
Thomas
T
Bonnard
1. Inserm, U698, Cardiovascular Bio-Engineering, X. Bichat hospital, 46 Rue H. Huchard, F-75018, Paris, France;
Gonord
G
Yang
3. IFR 02, UFR de Médecine, site Bichat, Université Paris Diderot, F-75018, Paris, France;
Anne
A
Petiet
1. Inserm, U698, Cardiovascular Bio-Engineering, X. Bichat hospital, 46 Rue H. Huchard, F-75018, Paris, France;
Véronique
V
Ollivier
4. UFR SMBH, Université Paris 13, Sorbonne Paris Cité, F-93000, Bobigny, France.
Oualid
O
Haddad
1. Inserm, U698, Cardiovascular Bio-Engineering, X. Bichat hospital, 46 Rue H. Huchard, F-75018, Paris, France;
Denis
D
Arnaud
1. Inserm, U698, Cardiovascular Bio-Engineering, X. Bichat hospital, 46 Rue H. Huchard, F-75018, Paris, France;
Liliane
L
Louedec
1. Inserm, U698, Cardiovascular Bio-Engineering, X. Bichat hospital, 46 Rue H. Huchard, F-75018, Paris, France;
Laure
L
Bachelet-Violette
1. Inserm, U698, Cardiovascular Bio-Engineering, X. Bichat hospital, 46 Rue H. Huchard, F-75018, Paris, France;
Sidi Mohammed
SM
Derkaoui
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;
Didier
D
Letourneur
1. Inserm, U698, Cardiovascular Bio-Engineering, X. Bichat hospital, 46 Rue H. Huchard, F-75018, Paris, France;
Cedric
C
Chauvierre
1. Inserm, U698, Cardiovascular Bio-Engineering, X. Bichat hospital, 46 Rue H. Huchard, F-75018, Paris, France;
Catherine
C
Le Visage
D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging / Q000378:metabolism; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging*; D001792:Blood Platelets / Q000378:metabolism; D006801:Humans; D008297:Male; D008863:Microspheres; D019007:P-Selectin / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013667:Technetium / Q000737:chemistry / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon
D019007:P-Selectin; D011134:Polysaccharides; D019275:Radiopharmaceuticals; D013667:Technetium; C007789:fucoidan
99mTc; Fucoidan; Ligand; P-Selectin; Radiolabeled.