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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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