Acoustic characterization and pharmacokinetic analyses of new nanobubble ultrasound contrast agents.
Acoustic characterization and pharmacokinetic analyses of new nanobubble ultrasound contrast agents.
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DOI：
10.1016/j.ultrasmedbio.2013.05.007
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发表时间：
2013-11
影响因子：
2.9
通讯作者：
Exner, Agata A.
中科院分区：
文献类型：
--
作者：
Wu, Hanping;Rognin, Nicolas G.;Krupka, Tianyi M.;Solorio, Luis;Yoshiara, Hiroki;Guenette, Gilles;Sanders, Christopher;Kamiyama, Naohisa;Exner, Agata A.
与临床使用的微泡超声造影剂相比，纳米级的气泡(或纳米气泡)可能会潜在地渗入显示更具渗透性的血管系统的肿瘤中，从而促进靶向分子成像和药物输送。我们团队最近提出了一种简单的策略，使用非离子表面活性剂Pluronic作为尺寸控制辅料来制备平均直径为200 nm的纳米气泡，其稳定性和回声性能与微气泡相当。这项研究的目的是在体外和体内对纳米气泡的性质进行深入的表征，并与Definity微泡进行比较。通过使用模拟组织的体模，体外实验测量了造影剂溶液的回声和造影剂随时间的溶解速度。在三种不同的谐波频率(8、6.2和3.5 MHz)下，纳米气泡比Definity微气泡的回声更强。Definity微泡的溶解速度也是纳米气泡的1.67倍。然后在小鼠皮下人类结直肠腺癌(LS174T)体内进行了药代动力学研究。分析造影剂团注后肝、肾、肿瘤的峰值增强和衰减率。在三个受试区(肿瘤、肝脏和肾脏)，纳米气泡和Definity组之间的峰值增强没有显著差异。然而，在第一个200-S快速初始阶段，肿瘤和肾脏中纳米气泡的衰减速度明显慢于Definity。肝脏的衰变率在初始阶段和晚期的三个感兴趣区之间没有显著差异。我们的结果表明，新型纳米气泡造影剂的稳定性和声学性能优于临床使用的Definity微气泡。肿瘤中纳米气泡洗出的速度较慢，表明气泡可能被困在肿瘤实质内。
In contrast to the clinically used microbubble ultrasound contrast agents, nanoscale bubbles (or nanobubbles) may potentially extravasate into tumors that exhibit more permeable vasculature, facilitating targeted molecular imaging and drug delivery. Our group recently presented a simple strategy using the non-ionic surfactant Pluronic as a size control excipient to produce nanobubbles with a mean diameter of 200 nm that exhibited stability and echogenicity on par with microbubbles. The objective of this study was to carry out an in-depth characterization of nanobubble properties as compared with Definity microbubbles, both in vitro and in vivo. Through use of a tissue-mimicking phantom, in vitro experiments measured the echogenicity of the contrast agent solutions and the contrast agent dissolution rate over time. Nanobubbles were found to be more echogenic than Definity microbubbles at three different harmonic frequencies (8, 6.2 and 3.5 MHz). Definity microbubbles also dissolved 1.67 times faster than nanobubbles. Pharmacokinetic studies were then performed in vivo in a subcutaneous human colorectal adenocarcinoma (LS174T) in mice. The peak enhancement and decay rates of contrast agents after bolus injection in the liver, kidney and tumor were analyzed. No significant differences were observed in peak enhancement between the nanobubble and Definity groups in the three tested regions (tumor, liver and kidney). However, the decay rates of nanobubbles in tumor and kidney were significantly slower than those of Definity in the first 200-s fast initial phase. There were no significant differences in the decay rate in the liver in the initial phase or in three regions of interest in the terminal phase. Our results suggest that the stability and acoustic properties of the new nanobubble contrast agents are superior to those of the clinically used Definity microbubbles. The slower washout of nanobubbles in tumors suggests potential entrapment of the bubbles within the tumor parenchyma.
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影响因子：
4.2
作者：
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通讯作者：
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影响因子：
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作者：
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