title: Brain tumor enhancement in magnetic resonance imaging at 3 tesla: intraindividual comparison of two high relaxivity macromolecular contrast media with a standard extracellular gd-chelate in a rat brain tumor model.
abstract: OBJECTIVE
  The aim of this study was to evaluate lesion enhancement (LE) and contrast-to-noise ratio (CNR) properties of P846, a new intermediate sized, high relaxivity Gd-based contrast agent at 3 Tesla in a rat brain glioma model, and to compare this contrast agent with a high relaxivity, macromolecular compound (P792), and a standard extracellular Gd-chelate (Gd-DOTA).
  
  
  METHODS
  Seven rats with experimental induced brain glioma were evaluated using 3 different contrast agents, with each MR examination separated by at least 24 hours. The time between injections assured sufficient clearance of the agent from the tumor, before the next examination. P792 (Gadomelitol, Guerbet, France) and P846 (a new compound from Guerbet Research) are macromolecular and high relaxivity contrast agents with no protein binding, and were compared with the extracellular agent Gd-DOTA (Dotarem, Guerbet, France). T1w gradient echo sequences (TR/TE 200 milliseconds/7.38 milliseconds, flip angle = 90 degrees , acquisition time: 1:42 minutes:sec, voxel size: 0.2 x 0.2 x 2.0 mm, FOV = 40 mm, acquisition matrix: 256 x 256) were acquired before and at 5 consecutive time points after each intravenous contrast injection in the identical slice orientation, using a dedicated 4-channel head array animal coil. The order of contrast media injection was randomized, with however Gd-DOTA used either as the first or second contrast agent. Contrast agent dose was adjusted to compensate for the different T1 relaxivities of the 3 agents. Signal-to-noise ratio, CNR, and LE were evaluated using region-of-interest analysis. A veterinary histopathologist confirmed the presence of a glioma in each subject, after completion of the imaging study.
  
  
  RESULTS
  P792 showed significantly less LE as compared with Gd-DOTA within the first 7 minutes after contrast agent injection (P < 0.05) with, however, reaching comparable LE values at 9 minutes after injection (P = 0.07). However, P792 provided significantly less CNR as compared with Gd-DOTA (P < 0.05) for all examination time points. P846 provided comparable but persistent LE as compared with Gd-DOTA (P < 0.05) and demonstrated significantly greater LE and CNR when compared with P792 (P < 0.05). No statistically significant differences between CNR values for Gd-DOTA and P846 were noted for all examination time points (P < 0.05), with P846 administered at one-fourth the dose as compared with Gd-DOTA.
  
  
  CONCLUSIONS
  The intravascular contrast medium P792 showed significantly less LE and CNR in comparison to Gd-DOTA and P846, suggesting that it does not show marked extravasation from tumor neocapillaries and does not significantly cross the disrupted blood brain-barrier in this rat glioma model. In distinction, P846 provides comparable enhancement properties at a field strength of 3 Tesla to the extracellular contrast agent Gd-DOTA, using the adjusted dose, suggesting that it crosses the disrupted blood-brain-barrier and tumor capillaries, most likely based on the decreased molecular weight as compared with P792. At the same time, the high relaxivity of this compound allows for decreasing the injected gadolinium dose by a factor of 4 whereas providing comparable enhancement properties when compared with a standard extracellular Gd-chelate (Gd-DOTA) at a dose of 0.1 mmol/kg body weight.
authors.affiliation: Clinic of Diagnostic and Interventional Radiology, Saarland University Hospital, Homburg, Germany. peter.fries@uks.eu
authors.forename: Peter
authors.initials: P
authors.lastname: Fries
authors.forename: Val M
authors.initials: VM
authors.lastname: Runge
authors.forename: Arno
authors.initials: A
authors.lastname: Bücker
authors.forename: Hellmut
authors.initials: H
authors.lastname: Schürholz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Reith
authors.forename: Philippe
authors.initials: P
authors.lastname: Robert
authors.forename: Carney
authors.initials: C
authors.lastname: Jackson
authors.forename: Titus
authors.initials: T
authors.lastname: Lanz
authors.forename: Günther
authors.initials: G
authors.lastname: Schneider
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000503:physiopathology; D002614:Chelating Agents / Q000737:chemistry*; D003287:Contrast Media / Q000737:chemistry*; D004195:Disease Models, Animal; D005260:Female; D005682:Gadolinium; D005910:Glioma / Q000473:pathology*; D046911:Macromolecular Substances; D008279:Magnetic Resonance Imaging; D008958:Models, Molecular; D011856:Radiographic Image Enhancement; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D046911:Macromolecular Substances; D005682:Gadolinium