Visualization of antigen-specific human cytotoxic T lymphocytes labeled with superparamagnetic iron-oxide particles.
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.
Beer
Ambros J
AJ
Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich (TUM), Munich, Germany.
Holzapfel
Konstantin
K
Neudorfer
Juliana
J
Piontek
Guido
G
Settles
Marcus
M
Krönig
Holger
H
Peschel
Christian
C
Schlegel
Jürgen
J
Rummeny
Ernst J
EJ
Bernhard
Helga
H
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
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide