Chen Feng, Goel Shreya, Hernandez Reinier, Graves Stephen A, Shi Sixiang, Nickles Robert J, Cai Weibo
Department of Radiology, University of Wisconsin-Madison, Madison, WI, 53705, USA.
Materials Science Program, University of Wisconsin-Madison, Madison, WI, 53705, USA.
Small. 2016 May;12(20):2775-82. doi: 10.1002/smll.201600194. Epub 2016 Apr 9.
Optical imaging has been the primary imaging modality for nearly all of the renal clearable nanoparticles since 2007. Due to the tissue depth penetration limitation, providing accurate organ kinetics non-invasively has long been a huge challenge. Although a more quantitative imaging technique has been developed by labeling nanoparticles with single-photon emission computed tomography (SPECT) isotopes, the low temporal resolution of SPECT still limits its potential for visualizing the rapid dynamic process of renal clearable nanoparticles in vivo. The dynamic positron emission tomography (PET) imaging of renal clearable gold (Au) nanoparticles by labeling them with copper-64 ((64) Cu) to form (64) Cu-NOTA-Au-GSH is reported. Systematic nanoparticle synthesis and characterizations are performed to demonstrate the efficient renal clearance of as-prepared nanoparticles. A rapid renal clearance of (64) Cu-NOTA-Au-GSH is observed (>75%ID at 24 h post-injection) with its elimination half-life calculated to be less than 6 min, over 130 times shorter than previously reported similar nanoparticles. Dynamic PET imaging not only addresses the current challenges in accurately and non-invasively acquiring the organ kinetics, but also potentially provides a highly useful tool for studying renal clearance mechanism of other ultra-small nanoparticles, as well as the diagnosis of kidney diseases in the near future.
自2007年以来,光学成像一直是几乎所有可经肾脏清除的纳米颗粒的主要成像方式。由于组织深度穿透限制,长期以来,无创提供准确的器官动力学一直是一项巨大挑战。尽管通过用单光子发射计算机断层扫描(SPECT)同位素标记纳米颗粒开发了一种更定量的成像技术,但SPECT的低时间分辨率仍然限制了其在体内可视化可经肾脏清除的纳米颗粒快速动态过程的潜力。本文报道了通过用铜-64(64Cu)标记可经肾脏清除的金(Au)纳米颗粒以形成64Cu-NOTA-Au-GSH进行动态正电子发射断层扫描(PET)成像。进行了系统的纳米颗粒合成和表征,以证明所制备的纳米颗粒具有高效的肾脏清除率。观察到64Cu-NOTA-Au-GSH的肾脏清除迅速(注射后24小时>75%注射剂量),其消除半衰期计算小于6分钟,比先前报道的类似纳米颗粒短130多倍。动态PET成像不仅解决了当前在准确无创获取器官动力学方面的挑战,而且有可能为研究其他超小纳米颗粒的肾脏清除机制以及在不久的将来诊断肾脏疾病提供一种非常有用的工具。