Gold nanoparticles: a new X-ray contrast agent

Gold nanoparticles: a new X-ray contrast agent
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DOI:
10.1259/bjr/13169882
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发表时间:
2006-03-01
影响因子:
2.6
通讯作者:
Smilowitz, HM
Smilowitz, HM
中科院分区:
医学3区
文献类型:
--
作者:
Hainfeld, JF;Slatkin, DN;Smilowitz, HM

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25年多来,临床X射线造影剂几乎没有根本性的改进,三碘苯的化学平台没有改变。目前的药物对医学成像造成了严重的限制:成像时间短,在许多情况下需要导管插入术,偶尔的肾毒性,以及大型患者的对比度差。本报告首次证明金纳米颗粒可以克服这些限制。与碘相比,金的吸收率更高,骨和组织干扰更少,在X射线剂量较低的情况下实现了更好的对比度。纳米颗粒比碘剂更慢地清除血液,允许更长的成像时间。将直径为1.9 nm的金纳米颗粒静脉注射到小鼠体内,并使用标准乳房X线摄影装置记录随时间推移的图像。用原子吸收法测定金的生物分布。在肝脏和脾脏中的保留较低,经肾脏消除。肾脏和肿瘤等器官的清晰度和空间分辨率都非常高。描绘了直径小于100 μ m的血管,从而使体内血管铸型成为可能。可以区分血管形成和血管生成增加的区域。当血液中最初含有10 mg Au ml(-1)时,小鼠行为无异常,并且在注射后11天和30天,血浆分析物和器官组织学均未显示任何毒性证据。金纳米粒子可用作X射线造影剂,其性质克服了碘基造影剂的一些显著限制。
There have been few fundamental improvements in clinical X-ray contrast agents in more than 25 years, and the chemical platform of tri-iodobenzene has not changed. Current agents impose serious limitations on medical imaging: short imaging times, the need for catheterization in many cases, occasional renal toxicity, and poor contrast in large patients. This report is the first demonstration that gold nanoparticles may overcome these limitations. Gold has higher absorption than iodine with less bone and tissue interference achieving better contrast with lower X-ray dose. Nanoparticles clear the blood more slowly than iodine agents, permitting longer imaging times. Gold nanoparticles, 1.9 nm in diameter, were injected intravenously into mice and images recorded over time with a standard mammography unit. Gold biodistribution was measured by atomic absorption. Retention in liver and spleen was low with elimination by the kidneys. Organs such as kidneys and tumours were seen with unusual clarity and high spatial resolution. Blood vessels less than 100 mu m in diameter were delineated, thus enabling in vivo vascular casting. Regions of increased vascularization and angiogenesis could be distinguished. With 10 mg Au ml(-1) initially in the blood, mouse behaviour was unremarkable and neither blood plasma analytes nor organ histology revealed any evidence of toxicity 11 days and 30 days after injection. Gold nanoparticles can be used as X-ray contrast agents with properties that overcome some significant limitations of iodine-based agents.