Koyasu Sho, Minor Hannah A, Asiedu Kingsley O, Choyke Peter L, Sato Noriko
Molecular Imaging Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Pharmaceuticals (Basel). 2025 Jun 15;18(6):897. doi: 10.3390/ph18060897.
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 (Zr)-oxine cell labeling method to compare the trafficking of monocytes and macrophages in vivo. Mouse bone marrow-derived monocytes and macrophages were each labeled with 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. 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. 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. This study demonstrates the usefulness of Zr-oxine PET in tracking monocyte-macrophage lineage cells, highlighting their distinct migration patterns and providing insights that could advance monocyte-centered cell therapies.
基于细胞的疗法在癌症和炎症性疾病的治疗中变得越来越重要；然而，利用单核细胞-巨噬细胞谱系细胞的疗法仍相对未得到充分探索。非侵入性细胞追踪有助于更好地了解此类细胞的命运，这对于发挥其治疗潜力至关重要。在此，我们采用锆 - 89（Zr）- 8 - 羟基喹啉细胞标记方法来比较单核细胞和巨噬细胞在体内的迁移情况。将小鼠骨髓来源的单核细胞和巨噬细胞分别用Zr - 8 - 羟基喹啉标记，并在体外评估它们的活力、放射性保留、趋化性和吞噬功能。将标记的细胞静脉注射到健康小鼠以及肉芽肿和同基因肿瘤的小鼠模型中。使用微型PET/CT监测细胞迁移，同时通过离体生物分布和流式细胞术进一步评估细胞向病变部位的募集情况。在培养长达7天的时间里，标记的细胞与未标记的细胞表现出相似的存活和增殖能力。虽然两者都保持吞噬功能，但与巨噬细胞相比，单核细胞表现出更高的CCL2驱动的趋化性。Zr - 8 - 羟基喹啉PET显示细胞最初在肺部积聚，随后在2 - 24小时内归巢到肝脏和脾脏，并在5天的观察期内持续存在。值得注意的是，单核细胞比巨噬细胞更快地迁移到肝脏和脾脏。在炎症和癌症模型中，与巨噬细胞相比，单核细胞在病变部位的积聚更高。这项研究证明了Zr - 8 - 羟基喹啉PET在追踪单核细胞 - 巨噬细胞谱系细胞方面的有用性，突出了它们独特的迁移模式，并提供了可推动以单核细胞为中心的细胞疗法发展的见解。
