Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with <sup>89</sup>Zr Radioisotope in Mice and Rats
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...
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| Format: | Article |
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MDPI AG
2022-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/6/1118 |
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| author | Hojun Choi Myung-Yoon Kim Dae-Hwan Kim Hanoul Yun Byung-Koo Oh Su-Bin Kim In-Ho Song Hyun-Soo Park Sang-Eun Kim Cheolhyoung Park Chulhee Choi |
| author_facet | Hojun Choi Myung-Yoon Kim Dae-Hwan Kim Hanoul Yun Byung-Koo Oh Su-Bin Kim In-Ho Song Hyun-Soo Park Sang-Eun Kim Cheolhyoung Park Chulhee Choi |
| author_sort | Hojun Choi |
| collection | DOAJ |
| description | 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 (<sup>89</sup>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 <sup>89</sup>Zr signals in the organs were lower in rats than in mice, suggesting a higher excretion rate of exosomes in rats. A prolonged <sup>89</sup>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 <sup>89</sup>Zr, indicating that exosomes might be rapidly taken up by cells and tissues. |
| first_indexed | 2024-03-09T22:46:55Z |
| format | Article |
| id | doaj.art-e034c7def49447afae14c08e646f5cb5 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T22:46:55Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-e034c7def49447afae14c08e646f5cb52023-11-23T18:28:27ZengMDPI AGPharmaceutics1999-49232022-05-01146111810.3390/pharmaceutics14061118Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with <sup>89</sup>Zr Radioisotope in Mice and RatsHojun Choi0Myung-Yoon Kim1Dae-Hwan Kim2Hanoul Yun3Byung-Koo Oh4Su-Bin Kim5In-Ho Song6Hyun-Soo Park7Sang-Eun Kim8Cheolhyoung Park9Chulhee Choi10ILIAS Biologics Inc., Daejeon 34014, KoreaILIAS Biologics Inc., Daejeon 34014, KoreaILIAS Biologics Inc., Daejeon 34014, KoreaILIAS Biologics Inc., Daejeon 34014, KoreaILIAS Biologics Inc., Daejeon 34014, KoreaDepartment of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, KoreaDepartment of Nuclear Medicine, Seoul National University Bundang Hospital 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam 13620, KoreaDepartment of Nuclear Medicine, Seoul National University Bundang Hospital 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam 13620, KoreaDepartment of Nuclear Medicine, Seoul National University Bundang Hospital 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam 13620, KoreaILIAS Biologics Inc., Daejeon 34014, KoreaILIAS Biologics Inc., Daejeon 34014, KoreaFor 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 (<sup>89</sup>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 <sup>89</sup>Zr signals in the organs were lower in rats than in mice, suggesting a higher excretion rate of exosomes in rats. A prolonged <sup>89</sup>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 <sup>89</sup>Zr, indicating that exosomes might be rapidly taken up by cells and tissues.https://www.mdpi.com/1999-4923/14/6/1118exosomebiodistributionpharmacokineticszirconiumpositron emission tomography/computed tomography |
| spellingShingle | Hojun Choi Myung-Yoon Kim Dae-Hwan Kim Hanoul Yun Byung-Koo Oh Su-Bin Kim In-Ho Song Hyun-Soo Park Sang-Eun Kim Cheolhyoung Park Chulhee Choi Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with <sup>89</sup>Zr Radioisotope in Mice and Rats Pharmaceutics exosome biodistribution pharmacokinetics zirconium positron emission tomography/computed tomography |
| title | Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with <sup>89</sup>Zr Radioisotope in Mice and Rats |
| title_full | Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with <sup>89</sup>Zr Radioisotope in Mice and Rats |
| title_fullStr | Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with <sup>89</sup>Zr Radioisotope in Mice and Rats |
| title_full_unstemmed | Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with <sup>89</sup>Zr Radioisotope in Mice and Rats |
| title_short | Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with <sup>89</sup>Zr Radioisotope in Mice and Rats |
| title_sort | quantitative biodistribution and pharmacokinetics study of gmp grade exosomes labeled with sup 89 sup zr radioisotope in mice and rats |
| topic | exosome biodistribution pharmacokinetics zirconium positron emission tomography/computed tomography |
| url | https://www.mdpi.com/1999-4923/14/6/1118 |
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