Chen Ting, Mori Yuki, Inui-Yamamoto Chizuko, Komai Yutaka, Tago Yoshiyuki, Yoshida Shinichi, Takabatake Yoshitsugu, Isaka Yoshitaka, Ohno Kohji, Yoshioka Yoshichika
Biofunctional Imaging Laboratory, WPI Immunology Frontier Research Center (WPI IFReC), Osaka University.
Functional Imaging Technology, Center for Information and Neural Networks (CiNet), National Institute of Information and Communications Technology (NICT) and Osaka University.
Magn Reson Med Sci. 2017 Oct 10;16(4):275-283. doi: 10.2463/mrms.mp.2016-0067. Epub 2017 Jan 30.
To investigate the biodistribution and retention properties of the new super paramagnetic iron oxide (new SPIO: mean hydrodynamic diameter, 100 nm) nanoparticles, which have concentrated polymer brushes in the outer shell and are difficult for phagocytes to absorb, and to compare the new SPIO with clinically approved SPIO (Resovist: mean hydrodynamic diameter, 57 nm).
16 male C57BL/6N mice were divided in two groups according to the administered SPIO (n = 8 for each group; intravenous injection does, 0.1 ml). In vivo magnetic resonance imaging (MRI) was performed before and one hour, one day, one week and four weeks after SPIO administration by two dimensional-the fast low angle shot (2D-FLASH) sequence at 11.7T. Ex vivo high-resolution images of fixed organs were also obtained by (2D-FLASH). After the ex vivo MRI, organs were sectioned and evaluated histologically to confirm the biodistribution of each particle precisely.
The new SPIO was taken up in small amounts by liver Kupffer cells and showed a unique in vivo MRI contrast pattern in the kidneys, where the signal intensity decreased substantially in the boundaries between cortex and outer medulla and between outer and inner medulla. We found many round dark spots in the cortex by ex vivo MRI in both groups. Resovist could be detected almost in the cortex. The shapes of the dark spots were similar to those observed in the new SPIO group. Transmission electron microscopy revealed that Resovist and the new SPIO accumulated in different cells of glomeruli, that is, endothelial and mesangial cells, respectively.
The new SPIO was taken up in small amounts by liver tissue and showed a unique MRI contrast pattern in the kidney. The SPIO were found in the mesangial cells of renal corpuscles. Our results indicate that the new SPIO may be potentially be used as a new contrast agent for evaluation of kidney function as well as immunune function.
研究新型超顺磁性氧化铁（新型SPIO：平均流体动力学直径为100 nm）纳米颗粒的生物分布和滞留特性，该纳米颗粒在外壳中有密集的聚合物刷，吞噬细胞难以吸收，并将新型SPIO与临床批准的SPIO（Resovist：平均流体动力学直径为57 nm）进行比较。
16只雄性C57BL/6N小鼠根据所给予的SPIO分为两组（每组n = 8；静脉注射剂量为0.1 ml）。在11.7T下，通过二维快速低角度激发（2D-FLASH）序列在SPIO给药前以及给药后1小时、1天、1周和4周进行体内磁共振成像（MRI）。还通过（2D-FLASH）获得固定器官的离体高分辨率图像。离体MRI后，将器官切片并进行组织学评估，以精确确认每个颗粒的生物分布。
新型SPIO被肝库普弗细胞少量摄取，并在肾脏中显示出独特的体内MRI对比模式，在皮质与外髓质之间以及外髓质与内髓质之间的边界处信号强度大幅降低。通过离体MRI，我们在两组的皮质中均发现了许多圆形黑点。Resovist几乎可以在皮质中检测到。黑点的形状与新型SPIO组中观察到的相似。透射电子显微镜显示，Resovist和新型SPIO分别积聚在肾小球的不同细胞中，即内皮细胞和系膜细胞。
新型SPIO被肝组织少量摄取，并在肾脏中显示出独特的MRI对比模式。在肾小体的系膜细胞中发现了SPIO。我们的结果表明，新型SPIO可能有潜力用作评估肾功能以及免疫功能的新型造影剂。
