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

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.