Magnetic labeling of activated microglia in experimental gliomas

Microglia, as intrinsic immunoeffector cells of the central nervous system (CNS), play a very sensitive, crucial role in the response to almost any br ain pathology where they are activated to a phagocytic state. Based on the characteristic features of activated microglia, we investigated whether the se cells can be visualized with magnetic resonance imaging (MRI) using ultr asmall superparamagnetic iron oxides (USPIOs). The hypothesis of this study was that MR microglia visualization could not only reveal the extent of th e tumor, but also allow for assessing the status of immunologic defense. Us ing USPIOs in cell culture experiments and in a rat glioma model, we showed that microglia can be labeled magnetically. Labeled microglia are detected by confocal microscopy within and around tumors in a typical border-like p attern. Quantitative in vitro studies revealed that microglia internalize a mounts of USPIOs that are significantly higher than those incorporated by t umor cells and astrocytes. Labeled microglia can be detected and quantified with MRI in cell phantoms, and the extent of the tumor can be seen in glio ma-bearing rats in vivo. We conclude that magnetic labeling of microglia pr ovides a potential tool for MRI of gliomas, which reflects tumor morphology precisely. Furthermore, the results suggest that MRI may yield functional data on the immunologic reaction of the CNS.