Kim Dongkyu, Park Sangjin, Lee Jae Hyuk, Jeong Yong Yeon, Jon Sangyong
Research Center for Biomolecular Nanotechnology, Department of Life Science, Gwangju Institute of Science and Technology (GIST), 1 Oryong-dong, Buk-gu, Gwangju 500-712, Republic of Korea.
J Am Chem Soc. 2007 Jun 20;129(24):7661-5. doi: 10.1021/ja071471p. Epub 2007 May 27.
Current computed tomography (CT) contrast agents such as iodine-based compounds have several limitations, including short imaging times due to rapid renal clearance, renal toxicity, and vascular permeation. Here, we describe a new CT contrast agent based on gold nanoparticles (GNPs) that overcomes these limitations. Because gold has a higher atomic number and X-ray absorption coefficient than iodine, we expected that GNPs can be used as CT contrast agents. We prepared uniform GNPs ( approximately 30 nm in diameter) by general reduction of HAuCl4 by boiling with sodium citrate. The resulting GNPs were coated with polyethylene glycol (PEG) to impart antibiofouling properties, which extends their lifetime in the bloodstream. Measurement of the X-ray absorption coefficient in vitro revealed that the attenuation of PEG-coated GNPs is 5.7 times higher than that of the current iodine-based CT contrast agent, Ultravist. Furthermore, when injected intravenously into rats, the PEG-coated GNPs had a much longer blood circulation time (>4 h) than Ultravist (<10 min). Consequently, CT images of rats using PEG-coated GNPs showed a clear delineation of cardiac ventricles and great vessels. On the other hand, relatively high levels of GNPs accumulated in the spleen and liver, which contain phagocytic cells. Intravenous injection of PEG-coated GNPs into hepatoma-bearing rats resulted in a high contrast ( approximately 2-fold) between hepatoma and normal liver tissue on CT images. These results suggest that PEG-coated GNPs can be useful as a CT contrast agent for a blood pool and hepatoma imaging.
当前的计算机断层扫描（CT）造影剂，如碘基化合物，存在若干局限性，包括由于快速经肾清除导致的成像时间短、肾毒性和血管渗透。在此，我们描述了一种基于金纳米颗粒（GNP）的新型CT造影剂，它克服了这些局限性。由于金的原子序数和X射线吸收系数高于碘，我们预期GNP可作为CT造影剂。我们通过用柠檬酸钠煮沸将HAuCl4进行一般还原制备了均匀的GNP（直径约30纳米）。所得的GNP用聚乙二醇（PEG）包被以赋予抗生物污损特性，这延长了它们在血流中的寿命。体外X射线吸收系数的测量表明，PEG包被的GNP的衰减比当前的碘基CT造影剂优维显高5.7倍。此外，当静脉注射到大鼠体内时，PEG包被的GNP的血液循环时间（>4小时）比优维显（<10分钟）长得多。因此，使用PEG包被的GNP的大鼠CT图像清晰显示了心室和大血管。另一方面，相对高水平的GNP积聚在含有吞噬细胞的脾脏和肝脏中。将PEG包被的GNP静脉注射到荷肝癌大鼠体内，在CT图像上肝癌组织与正常肝组织之间产生了高对比度（约2倍）。这些结果表明，PEG包被的GNP可作为用于血池和肝癌成像的CT造影剂。
