title: Time course of contrast enhancement by micro-CT with dedicated contrast agents in normal mice and mice with hepatocellular carcinoma: comparison of one iodinated and two nanoparticle-based agents.
abstract: OBJECTIVE
  The aim of the present study was to characterize the kinetics of two nanoparticle-based contrast agents for preclinical imaging, Exitron nano 6000 and Exitron nano 12000, and the iodinated agent eXIA 160 in both healthy mice and in a mouse model of hepatocellular carcinoma (HCC). Semiautomatic segmentation of liver lesions for estimation of total tumor load of the liver was evaluated in HCC mice.
  
  
  METHODS
  The normal time course of contrast enhancement was assessed in 15 healthy C57BL/6 mice. Imaging of tumor spread in the liver was evaluated in 15 mice harboring a transgenic HCC model (ASV-B mice). Automatic segmentation of liver lesions for determination of total tumor burden of the liver was tested in three additional ASV-B mice before and after an experimental therapy.
  
  
  RESULTS
  In healthy mice, clearance of the contrast agent from blood was completed within 3-4 hours for eXIA 160 and Exitron nano 6000, whereas complete blood clearance of Exitron nano 12000 required about 24 hours. eXIA 160 provided maximum liver contrast at 1 hour post injection (p.i.) followed by a continuous decline. Enhancement of liver contrast with Exitron nano 6000 and Exitron nano 12000 reached a plateau at about 4 hours p.i., which lasted until the end of the measurements at 96 hours p.i. Maximum contrast enhancement of the liver was not statistically different between Exitron nano 6000 and Exitron nano 12000, but was about three times lower for eXIA 160 (P < .05). Visually Exitron nano 12000 provided the best liver-to-tumor contrast. Semiautomatic liver and tumor segmentation was feasible after the administration of Exitron nano 12000 but did not work properly for the other two contrast agents.
  
  
  CONCLUSIONS
  Both nanoparticle-based contrast agents provided stronger and longer lasting contrast enhancement of healthy liver parenchyma. Exitron nano 12000 allowed automatic segmentation of tumor lesions for estimation of the total tumor load in the liver.
authors.affiliation: Clinic of Nuclear Medicine, University Medicine Charité, Berlin, Germany.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Rothe
authors.affiliation: Clinic of Hepatology and Gastroenterology, University Medicine Charité, Berlin, Germany; German Cancer Consortium, Deutsches Krebsforschungzentrum (DKFZ), Heidelberg, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Rudolph
authors.affiliation: Clinic of Hepatology and Gastroenterology, University Medicine Charité, Berlin, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Rohwer
authors.affiliation: Department of Radiology and Nuclear Medicine, Medical School, Otto-von-Guericke University, Magdeburg A.ö.R., Magdeburg, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Kupitz
authors.affiliation: Clinic of Nuclear Medicine, University Medicine Charité, Berlin, Germany.
authors.forename: Betina
authors.initials: B
authors.lastname: Gregor-Mamoudou
authors.affiliation: Clinic of Radiology, University Medical Center, Hamburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Derlin
authors.affiliation: Department of Radiology and Nuclear Medicine, Medical School, Otto-von-Guericke University, Magdeburg A.ö.R., Magdeburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Furth
authors.affiliation: Department of Radiology and Nuclear Medicine, Medical School, Otto-von-Guericke University, Magdeburg A.ö.R., Magdeburg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Amthauer
authors.affiliation: Clinic of Nuclear Medicine, University Medicine Charité, Berlin, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Brenner
authors.affiliation: Clinic of Nuclear Medicine, University Medicine Charité, Berlin, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Buchert
authors.affiliation: Clinic of Hepatology and Gastroenterology, University Medicine Charité, Berlin, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Cramer
authors.affiliation: Department of Radiology and Nuclear Medicine, Medical School, Otto-von-Guericke University, Magdeburg A.ö.R., Magdeburg, Germany. Electronic address: ivayla.apostolova@med.ovgu.de.
authors.forename: Ivayla
authors.initials: I
authors.lastname: Apostolova
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000000981:diagnostic imaging / Q000378:metabolism*; D003198:Computer Simulation; D003287:Contrast Media / Q000493:pharmacokinetics; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007455:Iodine / Q000493:pharmacokinetics*; D008113:Liver Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry*; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D003287:Contrast Media; D007455:Iodine
keywords: Micro-CT; contrast agents; contrast enhancement; hepatocellular carcinoma; mouse model