Abdominal aortic aneurysms targeted by functionalized polysaccharide microparticles: a new tool for SPECT imaging.
Abdominal aortic aneurysms targeted by functionalized polysaccharide microparticles: a new tool for SPECT imaging.
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DOI：
10.7150/thno.7757
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发表时间：
2014
期刊：
影响因子：
12.4
通讯作者：
Le Visage C
中科院分区：
文献类型：
--
作者：
Bonnard T;Yang G;Petiet A;Ollivier V;Haddad O;Arnaud D;Louedec L;Bachelet-Violette L;Derkaoui SM;Letourneur D;Chauvierre C;Le Visage C
如今，由于缺乏能够进行早期检测和破裂风险预测的技术，动脉瘤诊断受到限制。仍然需要新的非侵入性分子成像工具。在本研究中，我们提出了一种用于腹主动脉瘤 (AAA) 的创新 SPECT 诊断工具，该工具由注射用多糖微粒制成，该微粒用锝 99m (99mTc) 放射性标记，并用岩藻依聚糖（一种能够靶向 P-选择素的硫酸化多糖）进行功能化。 P-选择素是一种在活化的内皮细胞和血小板上表达的细胞粘附分子，可在动脉瘤的血栓以及其他血管病变中找到。通过交联多糖葡聚糖和普鲁兰多糖获得最大流体动力学直径为 4 µm 的微粒。它们用岩藻依聚糖进行功能化。通过流式细胞术评估了与人活化血小板的体外相互作用，结果表明岩藻依聚糖功能化微粒对活化血小板表达的 P-选择素具有特异性亲和力。对于体内 AAA 成像，微粒用 99mTc 进行放射性标记，并静脉注射到健康大鼠和通过主动脉壁灌注弹性蛋白酶获得的 AAA 大鼠中。通过 SPECT 成像对动物进行扫描。在 AAA 大鼠的腹主动脉中获得了强烈的对比增强，而在健康大鼠或注射非功能化对照微粒后的 AAA 大鼠中没有获得信号。组织学研究表明，功能化放射性标记多糖微粒位于 AAA 壁中，与 P-选择素表达的位置相同。因此，这些微粒构成了一种有前景的 SPECT 成像工具，可用于治疗 AAA，并有可能用于其他以 P-选择素表达为特征的血管疾病。未来的工作将集中于验证微粒诊断这些其他病理和 AAA 不同阶段的效率。还考虑掺入治疗分子。
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.
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影响因子：
14
作者：
Eniola, AO;Hammer, DA
通讯作者：
Hammer, DA
影响因子：
12.4
作者：
Choi KY;Swierczewska M;Lee S;Chen X
通讯作者：
Chen X
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3
作者：
Jung, Hyunsook;Robison, Aaron D.;Cremer, Paul S.
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作者：
Klink, Ahmed;Heynens, Joeri;Herranz, Beatriz;Lobatto, Mark E.;Arias, Teresa;Sanders, Honorius M. H. F.;Strijkers, Gustav J.;Merkx, Maarten;Nicolay, Klaas;Fuster, Valentin;Tedgui, Alain;Mallat, Ziad;Mulder, Willem J. M.;Fayad, Zahi A.
通讯作者：
Fayad, Zahi A.
影响因子：
14
作者：
Fricain, Jean Christophe;Schlaubitz, Silke;Amedee, Joelle
通讯作者：
Amedee, Joelle