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Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with (89)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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229812/ https://www.ncbi.nlm.nih.gov/pubmed/35745690 http://dx.doi.org/10.3390/pharmaceutics14061118 |
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author | 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 |
author_facet | 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 |
author_sort | Choi, Hojun |
collection | PubMed |
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 ((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 (89)Zr signals in the organs were lower in rats than in mice, suggesting a higher excretion rate of exosomes in rats. A prolonged (89)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 (89)Zr, indicating that exosomes might be rapidly taken up by cells and tissues. |
format | Online Article Text |
id | pubmed-9229812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92298122022-06-25 Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with (89)Zr Radioisotope in Mice and Rats 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 Pharmaceutics Article 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 ((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 (89)Zr signals in the organs were lower in rats than in mice, suggesting a higher excretion rate of exosomes in rats. A prolonged (89)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 (89)Zr, indicating that exosomes might be rapidly taken up by cells and tissues. MDPI 2022-05-24 /pmc/articles/PMC9229812/ /pubmed/35745690 http://dx.doi.org/10.3390/pharmaceutics14061118 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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 Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with (89)Zr Radioisotope in Mice and Rats |
title | Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with (89)Zr Radioisotope in Mice and Rats |
title_full | Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with (89)Zr Radioisotope in Mice and Rats |
title_fullStr | Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with (89)Zr Radioisotope in Mice and Rats |
title_full_unstemmed | Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with (89)Zr Radioisotope in Mice and Rats |
title_short | Quantitative Biodistribution and Pharmacokinetics Study of GMP-Grade Exosomes Labeled with (89)Zr Radioisotope in Mice and Rats |
title_sort | quantitative biodistribution and pharmacokinetics study of gmp-grade exosomes labeled with (89)zr radioisotope in mice and rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229812/ https://www.ncbi.nlm.nih.gov/pubmed/35745690 http://dx.doi.org/10.3390/pharmaceutics14061118 |
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