Feasibility study of68Ga-labeled CAR T cells for in vivo tracking using micro-positron emission tomography imaging
Feasibility study of68Ga-labeled CAR T cells for in vivo tracking using micro-positron emission tomography imaging
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DOI：
10.1038/s41401-020-00511-5
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发表时间：
2020-09-08
影响因子：
8.2
通讯作者：
Yang, Min
中科院分区：
文献类型：
--
作者：
Wang, Xin-yu;Wang, Yan;Yang, Min
通过正电子发射断层扫描(PET)成像对体内嵌合抗原受体(CAR)T细胞的临床跟踪是一个非常感兴趣的领域。但长寿的正电子发射体标记的CAR T细胞在肝脏和脾中停留数天甚至数周。因此，过高的吸收有效剂量成为一个主要的生物安全问题，导致其难以临床翻译。在这项研究中，我们使用了一种商用的短寿命正电子发射器Ga-68来标记CAR T细胞，用于体内的非侵入性细胞跟踪。~(68)Ga-PET可在体内示踪CAR T细胞至少6h，我们发现~(89)Zr和~(68)Ga标记的CAR T细胞在同一组织(肺、肝和脾)的分布显著相关。CAR T细胞早期的分布和归巢行为与CAR T细胞在体内的长期命运密切相关。~(68)Ga标记CAR T细胞的有效吸收剂量仅为()锆标记CAR T细胞的1/24，可安全用于临床移植。我们得出结论：在PET成像的基础上，(68)Ga替代(89)Zr直接标记CAR T细胞用于体内早期无创性示踪是可行的。这种方法为临床上对用于细胞追踪的安全和实用的PET示踪剂提供了潜在的解决方案。
Clinical tracking of chimeric antigen receptor (CAR) T cells in vivo by positron emission tomography (PET) imaging is an area of intense interest. But the long-lived positron emitter-labeled CAR T cells stay in the liver and spleen for days or even weeks. Thus, the excessive absorbed effective dose becomes a major biosafety issue leading it difficult for clinical translation. In this study we used Ga-68, a commercially available short-lived positron emitter, to label CAR T cells for noninvasive cell tracking in vivo. CAR T cells could be tracked in vivo by(68)Ga-PET imaging for at least 6 h. We showed a significant correlation between the distribution of(89)Zr and(68)Ga-labeled CAR T cells in the same tissues (lungs, liver, and spleen). The distribution and homing behavior of CAR T cells at the early period is highly correlated with the long-term fate of CAR T cells in vivo. And the effective absorbed dose of(68)Ga-labeled CAR T cells is only one twenty-fourth of(89)Zr-labeled CAR T cells, which was safe for clinical translation. We conclude the feasibility of(68)Ga instead of(89)Zr directly labeling CAR T cells for noninvasive tracking of the cells in vivo at an early stage based on PET imaging. This method provides a potential solution to the emerging need for safe and practical PET tracer for cell tracking clinically.