Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat.
Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat.
复制标题
大鼠Spion Microbubbles的生物分布，动力学和生物命运。
DOI：
10.2147/ijn.s49948
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发表时间：
2013
影响因子：
8
通讯作者：
Hassan M
中科院分区：
文献类型：
--
作者：
Barrefelt Å;Saghafian M;Kuiper R;Ye F;Egri G;Klickermann M;Brismar TB;Aspelin P;Muhammed M;Dähne L;Hassan M
在本研究中，我们研究了由聚（乙烯醇）（PVA）微泡组成的造影剂的动力学和生物分布，微泡含有捕获在 PVA 层之间的超顺磁性氧化铁（SPION）（SPION 微泡）。静脉注射后，在 Sprague-Dawley 大鼠中测定了 SPION 微泡的生物学命运。使用磁共振成像对大鼠进行了为期 6 周的微泡生物分布和消除研究。在不同时间点处死大鼠并进行灌注固定。将获得的磁共振成像结果与不同器官的组织病理学结果进行比较。注射后 10 分钟即可通过磁共振成像在肝脏中检测到 SPION 微泡。注射后 24 小时至 1 周之间检测到最大信号。组织病理学显示，从第一个研究时间点（10 分钟）开始，肺部就主要存在聚集的 SPION 微泡。随着时间的推移，肺血管系统中微泡的频率下降，而肺、肝和脾巨噬细胞中的微泡频率增加，导致从肺相对转移到脾和肝。与此同时，巨噬细胞显示出越来越多的细胞质铁积累迹象，最初是在肺部，然后是其他器官。本研究强调了 SPION 微泡的生物学行为，包括随时间的器官分布和生物降解迹象。目前的结果对于开发 SPION 微泡作为潜在的造影剂和/或特定器官的药物输送载体至关重要。这种车辆将促进多模态成像技术的使用，包括超声、磁共振成像和单正电子发射计算机断层扫描，从而改善诊断、治疗和监测治疗效果的能力。
In the present investigation, we studied the kinetics and biodistribution of a contrast agent consisting of poly(vinyl alcohol) (PVA) microbubbles containing superparamagnetic iron oxide (SPION) trapped between the PVA layers (SPION microbubbles). The biological fate of SPION microbubbles was determined in Sprague-Dawley rats after intravenous administration. Biodistribution and elimination of the microbubbles were studied in rats using magnetic resonance imaging for a period of 6 weeks. The rats were sacrificed and perfusion-fixated at different time points. The magnetic resonance imaging results obtained were compared with histopathologic findings in different organs. SPION microbubbles could be detected in the liver using magnetic resonance imaging as early as 10 minutes post injection. The maximum signal was detected between 24 hours and one week post injection. Histopathology showed the presence of clustered SPION microbubbles predominantly in the lungs from the first time point investigated (10 minutes). The frequency of microbubbles declined in the pulmonary vasculature and increased in pulmonary, hepatic, and splenic macrophages over time, resulting in a relative shift from the lungs to the spleen and liver. Meanwhile, macrophages showed increasing signs of cytoplasmic iron accumulation, initially in the lungs, then followed by other organs. The present investigation highlights the biological behavior of SPION microbubbles, including organ distribution over time and indications for biodegradation. The present results are essential for developing SPION microbubbles as a potential contrast agent and/or a drug delivery vehicle for specific organs. Such a vehicle will facilitate the use of multimodality imaging techniques, including ultrasound, magnetic resonance imaging, and single positron emission computed tomography, and hence improve diagnostics, therapy, and the ability to monitor the efficacy of treatment.