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.
