Biodistribution of 89Zr-oxine-labeled human bone marrow-derived mesenchymal stem cells by micro-PET/computed tomography imaging in Sprague-Dawley rats

Purpose To develop a method for labeling human bone marrow mesenchymal stem cells (hMSCs) with Zr-89-oxine to characterize the biodistribution characteristics of hMSCs in normal Sprague-Dawley (SD) rats in real-time by micro-PET-computed tomography (micro-PET/CT) imaging. Methods Zr-89-oxine complex was synthesized from Zr-89-oxalate and 8-hydroxyquinoline (oxine). After hMSCs were labeled with the Zr-89-oxine complex, the radioactivity retention, viability, proliferation, apoptosis, differentiation, morphology, and phenotype of labeled cells were assessed. The biodistribution of Zr-89-oxine-labeled hMSCs in SD rats was tracked in real-time by micro-PET/CT imaging. Results The cell labeling efficiency was 52.6 +/- 0.01%, and Zr-89-oxine was stably retained in cells (66.7 +/- 0.9% retention on 7 days after labeling). Compared with the unlabeled hMSCs, Zr-89-oxine labeling did not affect the biological characteristics of cells. Following intravenous administration in SD rats, labeled hMSCs mainly accumulated in the liver (7.35 +/- 1.41% ID/g 10 days after labeling, n = 6) and spleen (8.48 +/- 1.20% ID/g 10 days after labeling, n = 6), whereas intravenously injected Zr-89-oxalate mainly accumulated in the bone (4.47 +/- 0.35% ID/g 10 days after labeling, n = 3). Conclusion Zr-89-oxine labeling and micro-PET/CT imaging provide a useful and non-invasive method of assessing the biodistribution of cell therapy products in SD rats. The platform provides a foundation for us to further understand the mechanism of action and migration dynamics of cell therapy products.

Automated summary

This study developed a method to label human bone marrow mesenchymal stem cells (hMSCs) with Zr-89-oxine and characterized their biodistribution in rats using real-time micro-PET/CT imaging. The labeled hMSCs were mainly found in the liver and spleen, providing insights into the mechanism and migration dynamics of cell therapy products.