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小动物体内Tc-99m标记的人脐带间充质干细胞来源外泌体的单光子发射计算机断层扫描(SPECT)成像

In vivo SPECT imaging of Tc-99m radiolabeled exosomes from human umbilical-cord derived mesenchymal stem cells in small animals.

作者信息

Chung Yi-Hsiu, Ho Yi-Pei, Farn Shiou-Shiow, Tsai Wei-Cheng, Li Zhi-Xiang, Lin Tzou-Yien, Weng Chi-Chang

机构信息

Department of Medical Research and Development, Research Division, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.

Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan; Healthy Aging Research Center, Chang GungUniversity, Taoyuan, Taiwan.

出版信息

Biomed J. 2024 Oct;47(5):100721. doi: 10.1016/j.bj.2024.100721. Epub 2024 Apr 16.

DOI:10.1016/j.bj.2024.100721
PMID:38636899
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11401219/
Abstract

Extracellular vesicles derived from human umbilical cord-derived mesenchymal stem cells (UCMSC-EVs) have been postulated to have therapeutic potential for various diseases. However, the biodistribution and pharmacokinetics of these vesicles are still unclear. For a better understanding of the in vivo properties of UCMSC-EVs, in the present study, these vesicles were first radiolabeled with Technetium-99m (Tc-UCMSC-EVs) and evaluated using in vivo single photon emission computed tomography (SPECT) imaging and biodistribution experiments. SPECT images demonstrated that the liver and spleen tissues mainly took up the Tc-UCMSC-EVs. The biodistribution study observed slight uptake in the thyroid and stomach, indicating that Tc-UCMSC-EVs was stable at 24 h in vivo. The pharmacokinetic analyses of the blood half-life demonstrated the quick distribution phase (0.85 ± 0.28 min) and elimination phase (25.22 ± 20.76 min) in mice. This study provides a convenient and efficient method for Tc-UCMSC-EVs preparation without disturbing their properties. In conclusion, the biodistribution, quick elimination, and suitable stability in vivo of Tc-UCMSC-EVs were quantified by the noninvasive imaging and pharmacokinetic analyses, which provides useful information for indication selection, dosage protocol design, and toxicity assessment in future applications.

摘要

源自人脐带间充质干细胞的细胞外囊泡(UCMSC-EVs)被认为对多种疾病具有治疗潜力。然而,这些囊泡的生物分布和药代动力学仍不清楚。为了更好地了解UCMSC-EVs的体内特性,在本研究中,首先用锝-99m对这些囊泡进行放射性标记(Tc-UCMSC-EVs),并使用体内单光子发射计算机断层扫描(SPECT)成像和生物分布实验进行评估。SPECT图像显示,肝脏和脾脏组织主要摄取了Tc-UCMSC-EVs。生物分布研究观察到甲状腺和胃部有轻微摄取,表明Tc-UCMSC-EVs在体内24小时内是稳定的。血液半衰期的药代动力学分析表明,小鼠体内存在快速分布阶段(0.85±0.28分钟)和消除阶段(25.22±20.76分钟)。本研究提供了一种方便有效的Tc-UCMSC-EVs制备方法,且不会干扰其特性。总之,通过无创成像和药代动力学分析对Tc-UCMSC-EVs的生物分布、快速消除和体内合适的稳定性进行了量化,这为未来应用中的适应症选择、剂量方案设计和毒性评估提供了有用信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ec/11401219/aeb0475f2a6a/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ec/11401219/679d646333e9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ec/11401219/852275d55510/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ec/11401219/2fd082395ac9/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ec/11401219/cfc92f61e2b2/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ec/11401219/43a56935dbb1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ec/11401219/32adea4c0b44/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ec/11401219/aeb0475f2a6a/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ec/11401219/679d646333e9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ec/11401219/852275d55510/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ec/11401219/2fd082395ac9/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ec/11401219/cfc92f61e2b2/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ec/11401219/43a56935dbb1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ec/11401219/32adea4c0b44/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04ec/11401219/aeb0475f2a6a/gr7.jpg

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