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


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Kahts M., Guo H., Kommidi H., Yang Y., Sayman H. B., Summers B., ...More

EJNMMI Radiopharmacy and Chemistry, vol.8, no.1, 2023 (ESCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 8 Issue: 1
  • Publication Date: 2023
  • Doi Number: 10.1186/s41181-023-00223-1
  • Journal Name: EJNMMI Radiopharmacy and Chemistry
  • Journal Indexes: Emerging Sources Citation Index (ESCI), Scopus
  • Keywords: Cell trafficking, Infection imaging, Inflammation, PET, Zirconium-89
  • Istanbul University Affiliated: Yes

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.