First-in-human dosimetry and biodistribution of [89Zr]Zr-oxine-labeled autologous leukocytes using PET/CT

Purpose Cell tracking with zirconium-89 PET has the potential for widespread clinical and research applications, including imaging infection and inflammation and tracking cell-based therapies. This prospective first-in-human clinical trial assessed the dosimetry and safety profile of [ 89 Zr]Zr-oxine-labeled autologous leukocytes in healthy female participants. Methods Four healthy adult female participants (ages 37–53) received 10.9 ± 2.9 MBq of [ 89 Zr]Zr-oxine-labeled autologous leukocytes and underwent whole-body PET/CT imaging at five time points (0, 4, 24, 48, and 72 h). Regions of interest were automatically segmented on CT using a machine learning-based approach and manually refined. Time-integrated activity coefficients were calculated using Simpson’s rule, with physical decay assumed beyond the final time point. Mean absorbed-dose and effective-dose coefficients were estimated using OLINDA 2.1. Results Administration was well-tolerated among all participants. The highest mean absorbed-dose coefficients (mGy/MBq) with standard deviation were observed in the spleen (3.52 ± 1.38), liver (2.1 ± 0.45), adrenals (1.62 ± 0.24), uterus (1.48 ± 0.98), and kidneys (1.36 ± 0.12). The mean effective-dose coefficient was 0.92 ± 0.06 mSv/MBq, numerically lower than the predicted value of 1.14 mSv/MBq based on the distribution of [ 111 In]In-oxine-labeled leukocytes in adult females ( P = 0.006, one-sample t-test). The use of [ 89 Zr]Zr-oxine-labeled leukocytes enabled the visualization of leukocyte distribution and temporal dynamics. Conclusion This study demonstrates the safety and favorable dosimetry of [ 89 Zr]Zr-oxine-labeled leukocytes in healthy humans. These results support the further use of this approach for imaging autologous leukocytes using PET in a range of clinical and research settings. Trial registration ClinicalTrials.gov NCT03807973. Registered January 16, 2019.