89Zr-Leukocyte labelling for cell trafficking : in vitro and preclinical investigations

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Authors

Kahts, Maryke
Guo, Hua
Kommidi, Harikrishna
Yang, Yanping
Sayman, Haluk Burcak
Summers, Beverley
Ting, Richard
Zeevaart, Jan Rijn
Sathekge, Mike Machaba
Aras, Omer

Journal Title

Journal ISSN

Volume Title

Publisher

SpringerOpen

Abstract

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.

Description

ADDITIONAL 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.

Keywords

Cell trafficking, Infection imaging, Inflammation, Zirconium-89, Positron emission tomography (PET), SDG-03: Good health and well-being

Sustainable Development Goals

SDG-03:Good heatlh and well-being

Citation

Kahts, 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.