Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with Zr-89 Radioisotope in Mice and Rats

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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

Issue Date
Multidisciplinary Digital Publishing Institute (MDPI)
Pharmaceutics, Vol.14 No.6, p. 1118
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-89) 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-89 signals in the organs were lower in rats than in mice, suggesting a higher excretion rate of exosomes in rats. A prolonged Zr-89 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-89, indicating that exosomes might be rapidly taken up by cells and tissues.
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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