title: Visualization of antigen-specific human cytotoxic T lymphocytes labeled with superparamagnetic iron-oxide particles.
abstract: New technologies are needed to characterize the migration and survival of antigen-specific T cells in vivo. In this study, we developed a novel technique for the labeling of human cytotoxic T lymphocytes with superparamagnetic iron-oxide particles and the subsequent depiction with a conventional 1.5-T magnetic resonance scanner. Antigen-specific CD8(+) T lymphocytes were labeled with ferucarbotran by lipofection. The uptake of ferucarbotran was confirmed by immunofluorescence microscopy using a dextran-specific antibody, and the intracellular enrichment of iron was measured by atomic absorption spectrometry. The imaging of T cells was performed by magnetic resonance on day 0, 2, 7 and 14 after the labeling procedure. On day 0 and 2 post labeling, a pronounced shortening of T2*-relaxation times was observed, which diminished after 7 days and was not detectable anymore after 14 days, probably due to the retained mitotic activity of the labeled T cells. Of importance, the antigen-specific cytolytic activity of the T cells was preserved following ferucarbotran labeling. Efficient ferucarbotran labeling of functionally active T lymphocytes and their detection by magnetic resonance imaging allows the in vivo monitoring of T cells and, subsequently, will impact the further development of T cell-based therapies.
authors.affiliation: Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich (TUM), Munich, Germany.
authors.forename: Ambros J
authors.initials: AJ
authors.lastname: Beer
authors.forename: Konstantin
authors.initials: K
authors.lastname: Holzapfel
authors.forename: Juliana
authors.initials: J
authors.lastname: Neudorfer
authors.forename: Guido
authors.initials: G
authors.lastname: Piontek
authors.forename: Marcus
authors.initials: M
authors.lastname: Settles
authors.forename: Holger
authors.initials: H
authors.lastname: Krönig
authors.forename: Christian
authors.initials: C
authors.lastname: Peschel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schlegel
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Rummeny
authors.forename: Helga
authors.initials: H
authors.lastname: Bernhard
mesh_terms: D002460:Cell Line; D003287:Contrast Media / Q000493:pharmacokinetics*; D003911:Dextrans; D052203:Ferrosoferric Oxide; D006801:Humans; D007501:Iron / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008856:Microscopy, Fluorescence; D010087:Oxides / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D013054:Spectrophotometry, Atomic; D013194:Staining and Labeling; D013602:T-Lymphocytes, Cytotoxic
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide