Paramagnetic Gd3+ labeled red blood cells for magnetic resonance angiography

Paramagnetic Gd3+ labeled red blood cells for magnetic resonance angiography
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DOI:
10.1016/j.biomaterials.2016.05.002
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发表时间:
2016-08-01
期刊:
影响因子:
14
通讯作者:
Decuzzi, Paolo
Decuzzi, Paolo
中科院分区:
工程技术1区
文献类型:
--
作者:
Aryal, Santosh;Stigliano, Cinzia;Decuzzi, Paolo

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尽管对比增强磁共振血管造影术取得了重大进展,但缺乏具有长循环特性的真正血池剂限制了这种成像技术的临床影响。当静脉内给予肾功能正常的受试者时,大多数小分子量钆(Gd)基细胞外液剂的血液消除终末半衰期约为1.5小时。这些细胞外液剂的小尺寸不能阻止它们外渗,特别是从通常是高渗透性的受损血管外渗。因此,迫切需要开发新型的临床相关血池造影剂,以改善血管疾病的预防、检测和治疗结果。我们已经证明了融合策略,其中没有任何隐形特性的Gd-脂质体与红细胞(RBC)完全融合,形成MR发光的Gd-RBC,其循环半衰期(t(1/2)= 50 h)和Gd的弛豫率(r(1)= 19.0 mM(-1)s(-1))的数量级增加。用3 T临床MR扫描仪观察了Gd-RBC在活体内的长时间增强作用,可清晰显示腹主动脉。总之,血池剂的血管递送可受益于RBC的运载,因为它自然地停留在血管腔内。(C)2016爱思唯尔有限公司版权所有
Despite significant advances in contrast enhanced-magnetic resonance angiography, the lack of truly blood-pool agents with long circulating property is limiting the clinical impact of this imaging technique. The terminal half-life for blood elimination of most small molecular weight gadolinium (Gd) based extracellular fluid agents is about 1.5 h when administered intravenously to subjects with normal renal function. The small size of these extracellular fluid agents does not prevent them from extravasating, especially from damaged vessels which are generally hyperpermeable. Therefore, the development of novel, clinically relevant blood pool contrast agents is critically needed to improve outcomes in the prevention, detection, and treatment of vascular diseases. We have demonstrated the fusion strategies in which the Gd-liposome without any stealth property radically fuses with red blood cells (RBCs) forming MR glowing Gd-RBC with the order of magnitude enhancements in circulation half-life (t(1/2) = 50 h) and r(1) relaxivity (r(1) = 19.0 mM(-1) s(-1)) of Gd. The in vivo contrast enhancement of Gd-RBC was studied by using 3T clinical MR scanner for extended period of time, which clearly visualized the abdominal aorta. In summary, the vascular delivery of blood pool agents may benefit from carriage by RBCs because it naturally stays within the vascular lumen. (C) 2016 Elsevier Ltd. All rights reserved.