Abstract
37
Background: Accumulating evidence indicates endothelial progenitor cells (EPCs) play a major role in regulating pulmonary vascular remodeling during pulmonary arterial hypertension (PAH) development. However, there is no reliable method of real-time trafficking and quantification of transferred EPCs. We aimed to detect the homing of EPCs in health and PAH rats by 89Zr-oxine labeling PET imaging.
Methods: EPCs, isolated from human peripheral blood, was identified by specific EPCs biomarkers. The effect of 89Zr-oxine labeling on EPCs cell viability and proliferation was evaluated in vitro. 89Zr-labeled EPC cells (2 × 106 cells, 90 kBq/106 cells) were transferred intravenously to health and PAH rats and serial microPET/CT images were obtained.
Results: EPCs were characterized and efficiently labeled. In vitro viability and proliferation were not significantly reduced when labeled with 90 kBq per million cells. Intravenously administered 89Zr-labeled EPCs distributed primarily to the lung at 1 h and then subsequently migrated to the liver and spleen. The liver and spleen showed moderate accumulation with the highest %ID/g value of 5.30 ± 1.10 and 2.95 ± 0.54 at 72 h, respectively. The kidney and heart were also slightly visualized. Furthermore, microPET/CT results showed significantly higher accumulation of EPCs in lung of PAH than control group.
Conclusions: 89Zr-oxine can be used to delineate EPCs in lung of PAH by PET imaging and may provide a noninvasive EPCs monitoring tool. Figure legend A. Immunostaining and flow cytometric analysis of EPCs revealed expression of endothelial cell-specific markers CD31 (green), CD144 (green), and vWF (green), CD146 (red), KDR and the progenitor cell marker CD34. Nuclei were counterstained with DAPI (blue). Abbreviations: DAPI, 4,6-diamidino-2-phenylindole; vWF, von Willebrand factor; KDR, kinase insert domain receptor. B. Whole-body microPET/CT imaging of 89Zr-oxine EPCs in health rats. Maximum intensity projections (MIPs) of representative mice are shown at several time points after injection. C. Axial section showing the microPET/CT signal of 89Zr-oxine EPCs at the lung of the representative health and pulmonary arterial hypertension (PAH) rats. D. Quantification of PET images in the lung of health and PAH rats treated with 89Zr-oxine EPC cells over 10 days. Acknowledgments:This work was sponsored in part by the National Natural Science Foundation of China (Grant No. 81571713), Capital’s Funds for Health Improvement and Research(CFH) (Grant No. 2016-2-40115), CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No. 2016-I2M-4-003, 2017-I2M-3-001, 2018-I2M-3-001). No other potential conflicts of interest relevant to this article exist. <!--EndFragment-->