Zirconium-89-Oxine Cell Tracking by PET Reveals Preferential Monocyte Recruitment to Cancer and Inflammation over Macrophages

<b>Background/Objectives:</b> Cell-based therapies have become increasingly important in the treatment of cancers and inflammatory diseases; however, therapies utilizing monocyte–macrophage lineage cells remain relatively underexplored. Non-invasive cell tracking allows a better understa...

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Main Authors: Sho Koyasu, Hannah A. Minor, Kingsley O. Asiedu, Peter L. Choyke, Noriko Sato
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/18/6/897
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author Sho Koyasu
Hannah A. Minor
Kingsley O. Asiedu
Peter L. Choyke
Noriko Sato
author_facet Sho Koyasu
Hannah A. Minor
Kingsley O. Asiedu
Peter L. Choyke
Noriko Sato
author_sort Sho Koyasu
collection DOAJ
description <b>Background/Objectives:</b> Cell-based therapies have become increasingly important in the treatment of cancers and inflammatory diseases; however, therapies utilizing monocyte–macrophage lineage cells remain relatively underexplored. Non-invasive cell tracking allows a better understanding of the fate of such cells, which is essential for leveraging their therapeutic potential. Here, we employed a Zirconium-89 (<sup>89</sup>Zr)-oxine cell labeling method to compare the trafficking of monocytes and macrophages in vivo. <b>Methods:</b> Mouse bone marrow-derived monocytes and macrophages were each labeled with <sup>89</sup>Zr-oxine and evaluated for their viability, radioactivity retention, chemotaxis, and phagocytic function in vitro. Labeled cells were intravenously administered to healthy mice and to murine models of granuloma and syngeneic tumors. Cell migration was monitored using microPET/CT, while cell recruitment to the lesions was further assessed via ex vivo biodistribution and flow cytometry. <b>Results:</b> Labeled cells exhibited similar survival and proliferation to unlabeled cells for up to 7 days in culture. While both maintained phagocytic function, monocytes showed higher CCL2-driven chemotaxis compared to macrophages. <sup>89</sup>Zr-oxine PET revealed initial cell accumulation in the lungs, followed by their homing to the liver and spleen within 2–24 h, persisting through the 5-day observation period. Notably, monocytes trafficked to the liver and spleen more rapidly than macrophages. In both inflammation and cancer models, monocytes demonstrated higher accumulation at the lesion sites compared to macrophages. <b>Conclusions:</b> This study demonstrates the usefulness of <sup>89</sup>Zr-oxine PET in tracking monocyte–macrophage lineage cells, highlighting their distinct migration patterns and providing insights that could advance monocyte-centered cell therapies.
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spelling doaj-art-be4f35083f05461f9beb51319f0bf39e2025-08-20T02:21:49ZengMDPI AGPharmaceuticals1424-82472025-06-0118689710.3390/ph18060897Zirconium-89-Oxine Cell Tracking by PET Reveals Preferential Monocyte Recruitment to Cancer and Inflammation over MacrophagesSho Koyasu0Hannah A. Minor1Kingsley O. Asiedu2Peter L. Choyke3Noriko Sato4Molecular Imaging Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular Imaging Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular Imaging Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular Imaging Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAMolecular Imaging Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA<b>Background/Objectives:</b> Cell-based therapies have become increasingly important in the treatment of cancers and inflammatory diseases; however, therapies utilizing monocyte–macrophage lineage cells remain relatively underexplored. Non-invasive cell tracking allows a better understanding of the fate of such cells, which is essential for leveraging their therapeutic potential. Here, we employed a Zirconium-89 (<sup>89</sup>Zr)-oxine cell labeling method to compare the trafficking of monocytes and macrophages in vivo. <b>Methods:</b> Mouse bone marrow-derived monocytes and macrophages were each labeled with <sup>89</sup>Zr-oxine and evaluated for their viability, radioactivity retention, chemotaxis, and phagocytic function in vitro. Labeled cells were intravenously administered to healthy mice and to murine models of granuloma and syngeneic tumors. Cell migration was monitored using microPET/CT, while cell recruitment to the lesions was further assessed via ex vivo biodistribution and flow cytometry. <b>Results:</b> Labeled cells exhibited similar survival and proliferation to unlabeled cells for up to 7 days in culture. While both maintained phagocytic function, monocytes showed higher CCL2-driven chemotaxis compared to macrophages. <sup>89</sup>Zr-oxine PET revealed initial cell accumulation in the lungs, followed by their homing to the liver and spleen within 2–24 h, persisting through the 5-day observation period. Notably, monocytes trafficked to the liver and spleen more rapidly than macrophages. In both inflammation and cancer models, monocytes demonstrated higher accumulation at the lesion sites compared to macrophages. <b>Conclusions:</b> This study demonstrates the usefulness of <sup>89</sup>Zr-oxine PET in tracking monocyte–macrophage lineage cells, highlighting their distinct migration patterns and providing insights that could advance monocyte-centered cell therapies.https://www.mdpi.com/1424-8247/18/6/897monocytemacrophagecell tracking<sup>89</sup>Zr-oxinepositron emission tomographycell-based therapy
spellingShingle Sho Koyasu
Hannah A. Minor
Kingsley O. Asiedu
Peter L. Choyke
Noriko Sato
Zirconium-89-Oxine Cell Tracking by PET Reveals Preferential Monocyte Recruitment to Cancer and Inflammation over Macrophages
Pharmaceuticals
monocyte
macrophage
cell tracking
<sup>89</sup>Zr-oxine
positron emission tomography
cell-based therapy
title Zirconium-89-Oxine Cell Tracking by PET Reveals Preferential Monocyte Recruitment to Cancer and Inflammation over Macrophages
title_full Zirconium-89-Oxine Cell Tracking by PET Reveals Preferential Monocyte Recruitment to Cancer and Inflammation over Macrophages
title_fullStr Zirconium-89-Oxine Cell Tracking by PET Reveals Preferential Monocyte Recruitment to Cancer and Inflammation over Macrophages
title_full_unstemmed Zirconium-89-Oxine Cell Tracking by PET Reveals Preferential Monocyte Recruitment to Cancer and Inflammation over Macrophages
title_short Zirconium-89-Oxine Cell Tracking by PET Reveals Preferential Monocyte Recruitment to Cancer and Inflammation over Macrophages
title_sort zirconium 89 oxine cell tracking by pet reveals preferential monocyte recruitment to cancer and inflammation over macrophages
topic monocyte
macrophage
cell tracking
<sup>89</sup>Zr-oxine
positron emission tomography
cell-based therapy
url https://www.mdpi.com/1424-8247/18/6/897
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