gms | German Medical Science

Objective: Cell-tracking using MRI is most commonly done with iron-oxide particles. Gadofluorine M (GF) is a novel, non-iron-oxide contrast agent based on gadolinium with an amphiphilic character due to its perfluorinated side chain. In the underlying study we investigated whether the lipophilic properties of GF make labeling of malignant glioma cells in vitro feasible and enhance visualisation of glioma cells in MRI, which might be a helpful tool to track distribution patterns of tumor cells and tumor growth in vivo. Intracellular distribution of GF was analysed an proliferation and migration assays carried out to rule out adverse effects of GF on glioma cells.

Methods: U87-glioma cells were incubated with different concentrations of GF. Efficiency of the cell labeling process was analyzed by MRI. Fluorescence microscopic analyses and confocal laser scanning microscopy were used to demonstrate cellular uptake and to determine the intracellular distribution of Cy5-labeled GF. To ensure proper physiological function of GF-labeled cells, migration and proliferation assays were performed.

Results: We found that labeling of malignant glioma cells in vitro using Gadofluorine could easily be done without the need for special transfection agents or other additional means. Labeling of glioma cells with GF clearly enhanced visualisation of these cells in T1-weighted sequences, even after culturing cells in medium without GF. Significant loss of GF into the cell culture medium was ruled out by MRI. Confocal laser fluorescence microscopy revealed that Cy-5-labeled GF is localized in the perinuclear cytoplascmic region, but not within the nucleus nor bound to the cell membrane. Proliferation and migration of GF-labeled glioma cells was unchanged compared to unlabeled cells.

Conclusions: We conclude that Gadofluorine can easily be used to label glioma cells in vitro without significantly affecting glioma cell biology. Gadofluorine could represent an interesting alternative for cellular labelling in cases, where iron oxide particles are incorporated insufficiently by the target cells or if the vicinity to structures causing susceptibility artefacts prohibits the use of a signal-decreasing contrast agent.