Comparative in vivo biodistribution of cells labelled with [Zr-89]Zr-(oxinate)(4) or [Zr-89]Zr-DFO-NCS using PET

BackgroundIn vivo monitoring of cell biodistribution using positron emission tomography (PET) provides a quantitative non-invasive method to further optimize cell therapies and related new developments in the field. Our group has earlier optimized and evaluated the in vitro properties of two radiotracers,[Zr-89]Zr-(oxinate)(4) and [Zr-89]Zr-DFO-NCS, for the radiolabelling of different cell types. Here, we performed a microPET study to assess the in vivo biodistribution of cells in rats using these two radiotracers. Human decidual stromal cells (hDSC) and rat macrophages (rMac) were radiolabelled with [Zr-89]Zr-(oxinate)(4) or [Zr-89]Zr-DFO-NCS. Rats were intravenously injected with radiolabelled cells, and the in vivo biodistribution was monitored with microPET/CT imaging for up to day 7. Organ uptake was evaluated and presented as a percentage of injected activity per gram tissue (%IA/g) and total absorbed organ doses (mSv/MBq).ResultsThe biodistribution in vivo showed an immediate uptake in the lungs. Thereafter, [Zr-89]Zr-(oxinate)(4) labelled cells migrated to the liver, while the signal from [Zr-89]Zr-DFO-NCS labelled cells lingered in the lungs. The differences in the in vivo behaviour for the same cell type appeared related to the radiotracer labelling. After 24 h, [Zr-89]Zr-(oxinate)(4) labelled cells had over 70% higher liver uptake for both hDSC and rMac compared to [Zr-89]Zr-DFO-NCS labelled cells, whereas [Zr-89]Zr-DFO-NCS labelled cells showed over 60% higher uptake in the lungs compared to [Zr-89]Zr-(oxinate)(4) labelled cells. This difference in both lung and liver uptake continued until day 7. Dosimetry calculations showed a higher effective dose (mSv/MBq) for [Zr-89]Zr-DFO-NCS compared to [Zr-89]Zr-(oxinate)(4), for both cell types. Although the bone uptake was higher for [Zr-89]Zr-(oxinate)(4) labelled cells, the prolonged uptake in the lungs contributed to a significant crossfire to bone marrow resulting in a higher bone dose.ConclusionThe [Zr-89]Zr-DFO-NCS labelled cells suggest a prolonged accumulation in the lungs, while [Zr-89]Zr-(oxinate)(4) suggests quicker clearance of the lungs followed by accumulation in the liver. Accumulation of radiolabelled cells in the liver corresponds to other cell-tracking methods. Further studies are required to determine the actual location of the [Zr-89]Zr-DFO-NCS labelled cell.

Automated summary

The study assessed the in vivo biodistribution of cells in rats using two radiotracers, [Zr-89]Zr-(oxinate)(4) and [Zr-89]Zr-DFO-NCS. The results showed that the behavior of the radiolabelled cells in vivo was influenced by the labelling method. [Zr-89]Zr-(oxinate)(4) labelled cells had higher liver uptake, while [Zr-89]Zr-DFO-NCS labelled cells showed prolonged accumulation in the lungs. The difference in lung and liver uptake continued until day 7. Furthermore, dosimetry calculations showed different effective doses for the two radiotracers. The study highlights the importance of radiotracer labelling in cell biodistribution studies using PET.