Kahts, MarykeGuo, HuaKommidi, HarikrishnaYang, YanpingSayman, Haluk BurcakSummers, BeverleyTing, RichardZeevaart, Jan RijnSathekge, Mike MachabaAras, Omer2024-05-202024-05-202023-11-06Kahts, M., Guo, H., Kommidi, H. et al. 2023, '89Zr-Leukocyte labelling for cell trafficking : in vitro and preclinical investigations', EJNMMI Radiopharmacy and Chemistry, vol. 8, no. 36, pp. 1-16. https://DOI.org/10.1186/s41181-023-00223-1.2365-421X10.1186/s41181-023-00223-1http://hdl.handle.net/2263/96083ADDITIONAL FILE 1 : PET/CT images showing that intravenously introduced 89Zr-labelled leukocytes accumulated in the lung at 1 day and 5 days post injection, with slight migration to the liver over time. Free zirconium-89 accumulated in bone with no lung uptake. 5-week-old female Balb/c mice were intravenously injected with 0.22 MBq 89Zr-labelled leukocytes or free [ 89Zr]Zr4+ ion (control) and 30 min PET scans were performed at 1 day and 5 days post injection.DATA AVAILABILITY STATEMENT : The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.BACKGROUND : The non-invasive imaging of leukocyte trafficking to assess inflammatory areas and monitor immunotherapy is currently generating great interest. There is a need to develop more robust cell labelling and imaging approaches to track living cells. Positron emission tomography (PET), a highly sensitive molecular imaging technique, allows precise signals to be produced from radiolabelled moieties. Here, we developed a novel leukocyte labelling approach with the PET radioisotope zirconium- 89 (89Zr, half-life of 78.4 h). Experiments were carried out using human leukocytes, freshly isolated from whole human blood. RESULTS : The 89Zr-leukocyte labelling efficiency ranged from 46 to 87% after 30–60 min. Radioactivity concentrations of labelled cells were up to 0.28 MBq/1 million cells. Systemically administered 89Zr-labelled leukocytes produced highcontrast murine PET images at 1 h–5 days post injection. Murine biodistribution data showed that cells primarily distributed to the lung, liver, and spleen at 1 h post injection, and are then gradually trafficked to liver and spleen over 5 days. Histological analysis demonstrated that exogenously 89Zr-labelled human leukocytes were present in the lung, liver, and spleen at 1 h post injection. However, intravenously injected free [ 89Zr]Zr4+ ion showed retention only in the bone with no radioactivity in the lung at 5 days post injection, which implied good stability of radiolabelled leukocytes in vivo. CONCLUSIONS : Our study presents a stable and generic radiolabelling technique to track leukocytes with PET imaging and shows great potential for further applications in inflammatory cell and other types of cell trafficking studies.en© The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License.Cell traffickingInfection imagingInflammationZirconium-89Positron emission tomography (PET)SDG-03: Good health and well-beingArticle