title: In vitro evaluation of magnetic resonance imaging contrast agents for labeling human liver cells: implications for clinical translation.
abstract: OBJECTIVE
  Magnetic resonance imaging (MRI) is a promising approach for non-invasive monitoring after liver cell transplantation. We compared in vitro labeling of human liver cells with nano-sized (SPIO) and micron-sized iron oxide particles (MPIO).
  
  
  METHODS
  The cellular iron load was quantified and phantom studies were performed using 3.0-T MRI. Transferrin receptor and ferritin gene expression, reactive oxygen species (ROS) formation, transaminase leakage, and urea synthesis were investigated over 6 days.
  
  
  RESULTS
  Incubation with MPIO produced stronger signal extinctions in MRI at similar iron loads within shorter labeling time. MPIO had no negative effects on the cellular iron homeostasis or cell performance, whereas SPIO caused temporary ROS formation and non-physiologic activation of the iron metabolic pathway.
  
  
  CONCLUSIONS
  Our findings suggest that MPIO are suited for clinical translation of strategies for cellular imaging with MRI. Attention should be paid to iron release and oxidative stress caused by biodegradable contrast agents.
authors.affiliation: General, Visceral, and Transplantation Surgery, Experimental Surgery and Regenerative Medicine, Charité-Campus Virchow, Universitätsmedizin Berlin, Berlin, Germany. nathanael.raschzok@charite.de
authors.forename: Nathanael
authors.initials: N
authors.lastname: Raschzok
authors.forename: David A
authors.initials: DA
authors.lastname: Muecke
authors.forename: Michaela K
authors.initials: MK
authors.lastname: Adonopoulou
authors.forename: Nils
authors.initials: N
authors.lastname: Billecke
authors.forename: Wiebke
authors.initials: W
authors.lastname: Werner
authors.forename: Nora N
authors.initials: NN
authors.lastname: Kammer
authors.forename: Anja
authors.initials: A
authors.lastname: Zielinski
authors.forename: Peter A
authors.initials: PA
authors.lastname: Behringer
authors.forename: Frauke
authors.initials: F
authors.lastname: Ringel
authors.forename: Mao D
authors.initials: MD
authors.lastname: Huang
authors.forename: Peter
authors.initials: P
authors.lastname: Neuhaus
authors.forename: Ulf
authors.initials: U
authors.lastname: Teichgräber
authors.forename: Igor M
authors.initials: IM
authors.lastname: Sauer
mesh_terms: D003287:Contrast Media / Q000378:metabolism*; D005293:Ferritins / Q000235:genetics / Q000378:metabolism; D052203:Ferrosoferric Oxide / Q000378:metabolism; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000166:cytology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D013194:Staining and Labeling; D057170:Translational Research, Biomedical
chemical_list: D003287:Contrast Media; D017382:Reactive Oxygen Species; D011990:Receptors, Transferrin; D005293:Ferritins; D007501:Iron; D052203:Ferrosoferric Oxide