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

• Published in: Biomedical Journal Vol. 47; no. 5; p. 100721
• Main Authors: Chung, Yi-Hsiu, Ho, Yi-Pei, Farn, Shiou-Shiow, Tsai, Wei-Cheng, Li, Zhi-Xiang, Lin, Tzou-Yien, Weng, Chi-Chang
• Format: Journal Article
• Language: English
• Published: United States Elsevier B.V 01.10.2024; Chang Gung University
• Subjects: Biodistribution; Pharmacokinetic analyses; SPECT; Tc-99m; UCMSC-EVs; VSI: Extracellular Vesicles and Exosomes; Tc-99m; Pharmacokinetic analyses; UCMSC-EVs; Biodistribution; SPECT
• ISSN: 2319-4170; 2320-2890; 2320-2890
• DOI: 10.1016/j.bj.2024.100721

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 (99mTc-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 99mTc-UCMSC-EVs. The biodistribution study observed slight uptake in the thyroid and stomach, indicating that 99mTc-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 99mTc-UCMSC-EVs preparation without disturbing their properties. In conclusion, the biodistribution, quick elimination, and suitable stability in vivo of 99mTc-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. •The SPECT images demonstrated that 99mTc-UCMSC-EVs were mainly taken up by the liver and spleen and slightly in the lungs, joints, and spine. Moreover, the accumulation of 99mTc-UCMSC-EVs in the bladder implied that the kidneys could excrete this tracer. The pharmacokinetic analyses of the blood half-life demonstrated a 0.85 ± 0.28 min distribution phase and a 25.22 ± 20.76 min elimination phase. The upregulated expression of anti-CD73 in the spleen tissue corresponds to the autoradiogram image, which confirmed 99mTc-UCMSC-EV accumulation.