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 brain pathology where they are activated to a phagocytic state. Based on the characteristic features of activated microglia, we investigated whether these cells can be visualized with magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxides (USPIOs). The hypothesis of this study was that MR microglia visualization could not only reveal the extent of the tumor, but also allow for assessing the status of immunologic defense. Using 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 pattern. Quantitative in vitro studies revealed that microglia internalize amounts of USPIOs that are significantly higher than those incorporated by tumor 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 glioma-bearing rats in vivo. We conclude that magnetic labeling of microglia provides 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.
Fleige
G
G
Department of Radiology, Charité Medical School, Humboldt University of Berlin, Schumannstrasse 20/21, D-10117 Berlin, Germany. gerrit.fleige@charite.de
Nolte
C
C
Synowitz
M
M
Seeberger
F
F
Kettenmann
H
H
Zimmer
C
C
D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology*; D002478:Cells, Cultured / Q000166:cytology / Q000276:immunology; D003287:Contrast Media / Q000493:pharmacokinetics; D003911:Dextrans; D052203:Ferrosoferric Oxide; D005456:Fluorescent Dyes; D005910:Glioma / Q000276:immunology / Q000473:pathology*; D018316:Gliosarcoma / Q000276:immunology / Q000473:pathology; D007501:Iron / Q000493:pharmacokinetics; D017737:Macrophages, Peritoneal / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D058185:Magnetite Nanoparticles; D008297:Male; D017628:Microglia / Q000276:immunology*; D018613:Microscopy, Confocal; D009368:Neoplasm Transplantation; D010087:Oxides / Q000493:pharmacokinetics; D010587:Phagocytosis; D019047:Phantoms, Imaging; D051381:Rats; D011916:Rats, Inbred F344; D013194:Staining and Labeling; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000473:pathology; D014966:Xanthenes
D003287:Contrast Media; D003911:Dextrans; D005456:Fluorescent Dyes; D058185:Magnetite Nanoparticles; D010087:Oxides; D014966:Xanthenes; C097921:ferumoxtran-10; C034657:Texas red; D007501:Iron; D052203:Ferrosoferric Oxide