应用 SPECT 成像技术追踪缺血性脑卒中大鼠模型中 111In 标记的人脐带组织来源细胞（hUTC）的迁移。
Tracking of In-111-labeled human umbilical tissue-derived cells (hUTC) in a rat model of cerebral ischemia using SPECT imaging.
机构信息
Department of Radiology, Cellular and Molecular Imaging Laboratory, Henry Ford Hospital, Detroit, MI 48202, USA.
出版信息
BMC Med Imaging. 2012 Dec 6;12:33. doi: 10.1186/1471-2342-12-33.
BACKGROUND
In order to increase understanding of how infused cells work, it becomes important to track their initial movement, localization, and engraftment efficiency following transplantation. However, the available in vivo cell tracking techniques are suboptimal. The study objective was to determine the biodistribution of intravenously administered Indium-111 (In-111) oxine labeled human umbilical tissue-derived cells (hUTC) in a rat model of transient middle cerebral occlusion (tMCAo) using single photon emission computed tomography (SPECT).
METHODS
Rats received 3 million In-111 labeled hUTC (i.v.) 48 hrs after tMCAo. Following the administration of either hUTC or equivalent dose of In-111-oxine (18.5 MBq), animals underwent SPECT imaging on days 0, 1, and 3. Radioactivity in various organs as well as in the stroke area and contralateral hemisphere was determined, decay corrected and normalized to the total (whole body including head) radioactivity on day 0. Immunohistochemical analysis was also performed to confirm the beneficial effects of hUTC on vascular and synaptic density, and apoptosis.
RESULTS
Most of the radioactivity (43.36±23.07% on day 0) trafficked to the lungs immediately following IV administration of In-111 labeled hUTC (day 0) and decreased drastically to 8.81±7.75 and 4.01±4.52% on days 1 and 3 post-injection, respectively. In contrast, radioactivity measured in the lung of animals that received In-111-oxine alone remained relatively unchanged from day 0 to day 1 (18.38±5.45% at day 0 to 12.59±5.94%) and decreased to 8.34±4.25% on day 3. Significantly higher radioactivity was observed in stroke areas of animals that received In-111 labeled hUTC indicating the presence of cells at the site of injury representing approximately 1% of total administered dose. In addition, there was significant increase in vascular and synaptophysin immunoreactivity in stroke areas of rats that received In-111 labeled hUTC.
CONCLUSIONS
The present studies showed the tracking of In-111 labeled hUTC to the sites of stroke in a rat model of tMCAo using SPECT. Animals treated with In-111 labeled hUTC showed histological improvements, with higher vascular and synaptic densities observed in the ischemic boundary zone (IBZ).
背景
为了提高对输注细胞作用机制的理解，跟踪移植后细胞的初始运动、定位和植入效率变得尤为重要。然而，现有的细胞体内示踪技术并不理想。本研究旨在通过单光子发射计算机断层扫描（SPECT）确定静脉注射用铟-111（In-111）辛酸盐标记的人脐带组织来源细胞（hUTC）在短暂性大脑中动脉闭塞（tMCAo）大鼠模型中的分布。
方法
大鼠在 tMCAo 后 48 小时接受 300 万个 In-111 标记的 hUTC（静脉注射）。在给予 hUTC 或等效剂量的 In-111-辛酸盐（18.5MBq）后，动物在第 0、1 和 3 天进行 SPECT 成像。测定各器官以及梗塞区和对侧半球的放射性，校正衰减并将第 0 天的总放射性（包括头部的全身）归一化。还进行了免疫组织化学分析以确认 hUTC 对血管和突触密度以及细胞凋亡的有益作用。
结果
静脉注射 In-111 标记的 hUTC 后（第 0 天），大部分放射性（43.36±23.07%）立即转运到肺部，并在第 1 天和第 3 天分别急剧下降至 8.81±7.75%和 4.01±4.52%。相比之下，仅接受 In-111-辛酸盐的动物肺部的放射性从第 0 天到第 1 天基本保持不变（第 0 天为 18.38±5.45%，第 1 天为 12.59±5.94%），第 3 天下降至 8.34±4.25%。接受 In-111 标记的 hUTC 的动物梗塞区的放射性明显更高，表明细胞存在于损伤部位，代表给予剂量的约 1%。此外，在接受 In-111 标记的 hUTC 的大鼠梗塞区，血管和突触素免疫反应性明显增加。
结论
本研究使用 SPECT 显示了在 tMCAo 大鼠模型中跟踪铟-111 标记的 hUTC 到梗塞部位。用 In-111 标记的 hUTC 治疗的动物表现出组织学改善，在缺血边界区（IBZ）观察到更高的血管和突触密度。
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