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 89Zr-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: 89Zr-oxine complex was synthesized from 89Zr-oxalate and 8-hydroxyquinoline (oxine). After hMSCs were labeled with the 89Zr-oxine complex, the radioactivity retention, viability, proliferation, apoptosis, differentiation, morphology, and phenotype of labeled cells were assessed. The biodistribution of 89Zr-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 89Zr-oxine was stably retained in cells (66.7 ± 0.9% retention on 7 days after labeling). Compared with the unlabeled hMSCs, 89Zr-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 89Zr-oxalate mainly accumulated in the bone (4.47 ± 0.35% ID/g 10 days after labeling, n = 3).

Conclusion: 89Zr-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.