Magnetic resonance imaging targeting of intracranial glioma xenografts by Resovist-labeled endothelial progenitor cells.

Accumulating evidence suggests that endothelial progenitor cells (EPCs) play a key role in the development and infiltration of gliomas. Thus, it has been considered that EPCs may be good vehicles for delivering anti-angiogenesis genes for tumor therapy. However, limited means of tracking these cells in vivo has restricted the effective evaluation of the curative effects of genetically modified EPCs in gliomas at different stages. The aim of this study was to develop a non-invasive method to monitor the migration of EPCs to gliomas using 1.5-T MR scanning. We successfully labeled EPCs isolated from cord blood with Resovist-PLL without any influence on the biological properties of these cells. After intravenous administration into glioma-bearing nude mice, the labeled EPCs specifically homed to gliomas and could be reliably tracked by 1.5-T MR as early as 1 day after transplantation, causing a signal loss on T2-weighted images. The dark area was detected throughout the entire tumor zone on day 5, and did not develop a ring as previously described. Histological analysis showed the labeled cells were mainly located at the periphery of the tumor where abundant neo-vessels were identified using CD34 staining; this finding indicates that the transplanted cells may be able to differentiate into ECs and become incorporated into glioma neovasculature. These results suggested that Resovist labeling of EPCs is feasible, efficient and safe for MRI tracking, and 1.5-T MR could be a powerful method for in vivo monitoring of EPCs as an anti-angiogenic drug therapy vector targets against glioma.