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

Ida Friberger; Joachim N Nilsson; Li Lu; Jonathan Siikanen; Oscar Ardenfors; Stefan Milton; Erik Samén; Jeroen A C M Goos; Mattias Carlsten; Staffan Holmin; Thuy A Tran

doi:10.1186/s13550-023-01021-1

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

EJNMMI Res. 2023 Aug 8;13(1):73. doi: 10.1186/s13550-023-01021-1.

Authors

Ida Friberger¹, Joachim N Nilsson^{2

3}, Li Lu⁴, Jonathan Siikanen^{2

5}, Oscar Ardenfors², Stefan Milton^{4

5}, Erik Samén^{5

6}, Jeroen A C M Goos^{4

5

6}, Mattias Carlsten^{7

8}, Staffan Holmin^{4

9}, Thuy A Tran^{4

5

6}

Affiliations

¹ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. ida.friberger@ki.se.
² Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden.
³ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
⁴ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁵ Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
⁶ Department of Radiopharmacy, Karolinska University Hospital, Stockholm, Sweden.
⁷ Center for Hematology and Regenerative Medicine (HERM), Karolinska Institutet, Stockholm, Sweden.
⁸ Centre for Cell Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden.
⁹ Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden.

Abstract

Background: In 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,[⁸⁹Zr]Zr-(oxinate)₄ and [⁸⁹Zr]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 [⁸⁹Zr]Zr-(oxinate)₄ or [⁸⁹Zr]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).

Results: The biodistribution in vivo showed an immediate uptake in the lungs. Thereafter, [⁸⁹Zr]Zr-(oxinate)₄ labelled cells migrated to the liver, while the signal from [⁸⁹Zr]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, [⁸⁹Zr]Zr-(oxinate)₄ labelled cells had over 70% higher liver uptake for both hDSC and rMac compared to [⁸⁹Zr]Zr-DFO-NCS labelled cells, whereas [⁸⁹Zr]Zr-DFO-NCS labelled cells showed over 60% higher uptake in the lungs compared to [⁸⁹Zr]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 [⁸⁹Zr]Zr-DFO-NCS compared to [⁸⁹Zr]Zr-(oxinate)₄, for both cell types. Although the bone uptake was higher for [⁸⁹Zr]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.

Conclusion: The [⁸⁹Zr]Zr-DFO-NCS labelled cells suggest a prolonged accumulation in the lungs, while [⁸⁹Zr]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 [⁸⁹Zr]Zr-DFO-NCS labelled cell.

Keywords: 89Zr; Cell tracking; DSC; Deferoxamine; Dosimetry; Macrophages; Oxine; PET.