Feasibility study of 68Ga-labeled CAR T cells for in vivo tracking using micro-positron emission tomography imaging

Xin-yu Wang1, Yan Wang2,3, Qiong Wu1, Jing-jing Liu1, Yu Liu1, Dong-hui Pan1, Wei Qi4, Li-zhen Wang1, Jun-jie Yan1, Yu-ping Xu1, Guang-ji Wang5, Li-yan Miao2,3, Lei Yu4, Min Yang1
1 NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China
2 Department of Clinical Pharmacology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
3 Institute for Interdisciplinary Drug Research and Translational Sciences, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
4 School of Chemistry and Molecular Engineering, East China Normal University, Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd., Shanghai 200062, China
5 Key Laboratory of Drug Metabolismand Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China
Correspondence to: Li-yan Miao:, Lei Yu:, Min Yang:,
DOI: 10.1038/s41401-020-00511-5
Received: 14 May 2020
Accepted: 17 August 2020
Advance online: 8 September 2020


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 68Ga, 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 68Ga-PET imaging for at least 6 h. We showed a significant correlation between the distribution of 89Zr and 68Ga-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 68Ga-labeled CAR T cells is only one twenty-fourth of 89Zr-labeled CAR T cells, which was safe for clinical translation. We conclude the feasibility of 68Ga instead of 89Zr 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.
Keywords: CAR T; Gallium-68; Zirconium-89; positron emission tomography; cell tracking; noninvasive imaging

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