title: In vitro labeling of glioma cells with gadofluorine M enhances T1 visibility without affecting glioma cell growth or motility.
abstract: Gadofluorine is a novel macrocyclic, amphiphilic gadolinium-based contrast agent. We found that malignant glioma cells could be labeled in vitro using Gadofluorine without the need for transfection agents or any other additional means. Labeling with Gadofluorine enhanced the visualization of glioma cells in T(1)-weighted sequences, even if the cells had been cultured in medium without Gadofluorine over several days. The intracellular uptake of Gadofluorine was measured and the loss of relevant amounts of Gadofluorine into the cell culture medium was ruled out by MRI. Confocal laser fluorescence microscopy revealed Cy-5-labeled Gadofluorine in the perinuclear cytoplasmic region, but neither within the nucleus nor bound to the cell membrane. Adverse effects of cellular Gadofluorine uptake were ruled out by proliferation and migration assays. Finally, in vivo analyses provided good visibility of labeled glioma cells in T(1)-weighted sequences after intracerebral injection in mice for more than 2 weeks. We thus conclude that Gadofluorine can easily be used to label glioma cells in vitro without affecting glioma cell biology. Gadofluorine provides an interesting alternative for cellular labeling if iron oxide particles are incorporated insufficiently by target cells or if the vicinity of susceptibility artifacts prohibits the use of signal-decreasing contrast agents.
authors.affiliation: Department of Neuroradiology, University of Heidelberg, Medical Faculty Mannheim,Theodor-Kutzer-Ufer 1-3, Mannheim, Germany.
authors.forename: Ingo S
authors.initials: IS
authors.lastname: Nolte
authors.forename: Sevil
authors.initials: S
authors.lastname: Gungor
authors.forename: Ralf
authors.initials: R
authors.lastname: Erber
authors.forename: Elena
authors.initials: E
authors.lastname: Plaxina
authors.forename: Johann
authors.initials: J
authors.lastname: Scharf
authors.forename: Bernd
authors.initials: B
authors.lastname: Misselwitz
authors.forename: Lars
authors.initials: L
authors.lastname: Gerigk
authors.forename: Heike
authors.initials: H
authors.lastname: Przybilla
authors.forename: Christoph
authors.initials: C
authors.lastname: Groden
authors.forename: Marc A
authors.initials: MA
authors.lastname: Brockmann
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003287:Contrast Media / Q000493:pharmacokinetics*; D005466:Fluorocarbons; D019786:Gadolinium DTPA; D005910:Glioma / Q000473:pathology*; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009942:Organometallic Compounds / Q000493:pharmacokinetics*
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; D009942:Organometallic Compounds; C517961:gadofluorine M; D019786:Gadolinium DTPA