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Abstract
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 (89Zr) 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 89Zr signals in the organs were lower in rats than in mice, suggesting a higher excretion rate of exosomes in rats. A prolonged 89Zr 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 89Zr, indicating that exosomes might be rapidly taken up by cells and tissues.

Affiliations

Hojun Choi  1 , Myung-Yoon Kim  1 , Dae-Hwan Kim  1 , Hanoul Yun  1 , Byung-Koo Oh  1 , Su-Bin Kim  2   3 , In-Ho Song  3 , Hyun-Soo Park  3   4 , Sang-Eun Kim  3   4   5 , Cheolhyoung Park  1 , Chulhee Choi  1   6
1 ILIAS Biologics Inc., Daejeon 34014, Korea.
2 Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
3 Department of Nuclear Medicine, Seoul National University Bundang Hospital 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam 13620, Korea.
4 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea.
5 Advanced Institutes of Convergence Technology 145, Gwanggyo-ro, Yeongtong-gu, Suwon 16229, Korea.
6 Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.