title: Ytterbium- and dysprosium-EOB-DTPA. A new prototype of liver-specific contrast agents for computed tomography.
abstract: OBJECTIVE
  A series of studies was conducted to determine whether metal complexes of the EOB-DTPA type are useful as contrast agents for computed tomography (CT).
  
  
  METHODS
  Metal complexes using EOB-DTPA as ligand were synthesized with lanthanide metal ions (lanthanum [La], cerium [Ce], praseodyme [Pr], gadolinium [Gd], dysprosium [Dy], ytterbium [Yb], and lutetium [Lu]) and with nonlanthanides (lead [Pb] and bismuth [Bi]). Complex stability was assessed by measuring binding to bone meal. The physicochemical parameters partition coefficient, osmolality, viscosity, and protein binding were determined in vitro. Tolerability was tested both in vitro (thromboplastin time, effect on erythrocytes) and in vivo (acute, neural, and cardiovascular toxicities). Biliary excretion and tissue distribution, especially liver, kidney, and bone concentrations, were measured in rats after intravenous doses of 0.5 mmol/kg. Imaging performance using CT was investigated in vitro in a phantom model and, for Gd-EOB-DTPA, in vivo by injecting doses of 0.5 mmol/kg into healthy or tumor-bearing rats and rabbits.
  
  
  RESULTS
  The kinetic stability of M-EOB-DTPA complexes differed widely. Nonlanthanide metals, especially Pb-EOB-DTPA, provided less stable complexes than lanthanides with an optimum of stability for the metals Gd, Dy, Yb, and Lu. Tolerability was good for all compounds, best results were obtained for Gd and Yb. Concentrations in rat liver after administration of Gd-EOB-DTPA, 0.5 mmol/kg intravenous, were approximately 1 mumol/g, resulting in CT enhancement of 16 Hounsfield units (HU). Tumor tissue was not enhanced. In rabbits, at the same dose level 30 HU was found.
  
  
  CONCLUSIONS
  Metal complexes of the EOB-DTPA type, especially those of Gd and Yb seem to be useful as iodine-free liver-specific contrast agents for CT.
authors.affiliation: Research Laboratories, Schering AG, Berlin, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Krause
authors.forename: G
authors.initials: G
authors.lastname: Schuhmann-Giampieri
authors.forename: M
authors.initials: M
authors.lastname: Bauer
authors.forename: W R
authors.initials: WR
authors.lastname: Press
authors.forename: P
authors.initials: P
authors.lastname: Muschick
mesh_terms: D000818:Animals; D001688:Biological Products; D001729:Bismuth / Q000737:chemistry; D001842:Bone and Bones / Q000737:chemistry; D002563:Cerium / Q000737:chemistry; D002614:Chelating Agents / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics; D004419:Dysprosium / Q000737:chemistry / Q000493:pharmacokinetics; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D007811:Lanthanum / Q000737:chemistry; D007854:Lead / Q000737:chemistry; D008099:Liver / Q000000981:diagnostic imaging* / Q000378:metabolism; D008187:Lutetium / Q000737:chemistry; D008903:Minerals / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D009994:Osmolar Concentration; D010314:Partial Thromboplastin Time; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D019047:Phantoms, Imaging; D011221:Praseodymium / Q000737:chemistry; D011485:Protein Binding; D011817:Rabbits; D011856:Radiographic Image Enhancement / Q000379:methods; D051381:Rats; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D014783:Viscosity; D015018:Ytterbium / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D001688:Biological Products; D002614:Chelating Agents; D003287:Contrast Media; D008903:Minerals; D009942:Organometallic Compounds; D004419:Dysprosium; C073846:ytterbium DTPA; D007854:Lead; D002563:Cerium; D008187:Lutetium; D007811:Lanthanum; D004369:Pentetic Acid; C055865:dysprosium DTPA; D015018:Ytterbium; D011221:Praseodymium; C027762:bone meal; D001729:Bismuth