Choi Hojun, Kim Myung-Yoon, Kim Dae-Hwan, Yun Hanoul, Oh Byung-Koo, Kim Su-Bin, Song In-Ho, Park Hyun-Soo, Kim Sang-Eun, Park Cheolhyoung, Choi Chulhee
ILIAS Biologics Inc., Daejeon 34014, Korea.
Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
Pharmaceutics. 2022 May 24;14(6):1118. doi: 10.3390/pharmaceutics14061118.
For the successful clinical advancement of exosome therapeutics, the biodistribution and pharmacokinetic profile of exogenous exosomes in various animal models must be determined. Compared with fluorescence or bioluminescence imaging, radionuclide imaging confers multiple advantages for the in vivo tracking of biomolecular therapeutics because of its excellent sensitivity for deep tissue imaging and potential for quantitative measurement. Herein, we assessed the quantitative biodistribution and pharmacokinetics of good manufacturing practice-grade therapeutic exosomes labeled with zirconium-89 (Zr) after systemic intravenous administration in mice and rats. Quantitative biodistribution analysis by positron emission tomography/computed tomography and gamma counting in mice and rats revealed that the total Zr signals in the organs were lower in rats than in mice, suggesting a higher excretion rate of exosomes in rats. A prolonged Zr signal for up to 7 days in most organs indicated that substantial amounts of exosomes were taken up by the parenchymal cells in those organs, highlighting the therapeutic potential of exosomes for the intracellular delivery of therapeutics. Exosomes were mainly distributed in the liver and to a lesser extent in the spleen, while a moderately distributed in the kidney, lung, stomach, intestine, urinary bladder, brain, and heart. Exosomes were rapidly cleared from the blood circulation, with a rate greater than that of free Zr, indicating that exosomes might be rapidly taken up by cells and tissues.
为了使外泌体疗法在临床上取得成功进展，必须确定外源性外泌体在各种动物模型中的生物分布和药代动力学特征。与荧光或生物发光成像相比，放射性核素成像在生物分子疗法的体内追踪方面具有多种优势，因为它对深部组织成像具有出色的灵敏度且具有定量测量的潜力。在此，我们评估了在小鼠和大鼠全身静脉注射后，用锆 - 89（Zr）标记的药品生产质量管理规范级治疗性外泌体的定量生物分布和药代动力学。通过正电子发射断层扫描/计算机断层扫描和γ计数对小鼠和大鼠进行的定量生物分布分析表明，大鼠器官中的总Zr信号低于小鼠，这表明大鼠中外泌体的排泄率更高。大多数器官中Zr信号长达7天的延长表明大量外泌体被这些器官中的实质细胞摄取，突出了外泌体在细胞内递送治疗药物方面的治疗潜力。外泌体主要分布在肝脏，在脾脏中的分布较少，而在肾脏、肺、胃、肠道、膀胱、大脑和心脏中分布适中。外泌体从血液循环中迅速清除，清除速率高于游离Zr，这表明外泌体可能会迅速被细胞和组织摄取。
