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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 high-contrast 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.

Original languageEnglish
Article number36
JournalEJNMMI Radiopharmacy and Chemistry
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 2023

Keywords

  • Cell trafficking
  • Infection imaging
  • Inflammation
  • PET
  • Zirconium-89

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