title: Evaluation of gadobutrol, a macrocyclic, nonionic gadolinium chelate in a brain glioma model: comparison with gadoterate meglumine and gadopentetate dimeglumine at 1.5 T, combined with an assessment of field strength dependence, specifically 1.5 versus 3 T.
abstract: OBJECTIVE
  To evaluate in a rat brain glioma model intraindividual tumor enhancement at 1.5 T using gadobutrol (Gadovist), a nonionic, macrocyclic chelate currently in clinical trials in the United States, in comparison with both an ionic macrocyclic chelate, gadoterate meglumine (Dotarem), and an ionic linear chelate, gadopentetate dimeglumine (Magnevist), and to compare the degree of tumor enhancement with gadobutrol at 1.5 and 3 T.
  
  
  METHODS
  A total of 24 rats, divided into three groups with n = 8 animals per group, were evaluated. Animals in group 1 received injections of gadobutrol and gadopentetate dimeglumine, whereas those in group 2 received gadobutrol and gadoterate meglumine. Injections were performed in random order and separated by 24 hours. Magnetic resonance imaging (MRI) examinations were performed immediately following each contrast injection with a 1.5 T MR system. Animals in group 3 received gadobutrol injections using the same protocol but with scans performed at 1.5 and 3 T. In all examinations, T1-weighted images were acquired precontrast, 1 minute postcontrast, and at 4 consecutive 2-minute intervals thereafter. A contrast dose of 0.1 mmol/kg was used in all instances.
  
  
  RESULTS
  In groups 1 and 2, tumor signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were higher for gadobutrol compared to both other agents at each timepoint postcontrast injection. The improvement in tumor CNR with gadobutrol, depending on time, was between 12% and 40% versus gadopentetate dimeglumine, with the difference achieving statistical significance at 7 minutes. The improvement in tumor CNR with gadobutrol, depending on time, was between 15% and 27% versus gadoterate meglumine, with the difference statistically significant at 5 and 9 minutes. In group 3 the improvement in tumor SNR and CNR seen with the increase in field strength from 1.5 to 3 T for gadobutrol was statistically significant at all acquired timepoints (P < 0.002). CNR mean values ranged from 10.4 +/- 2.9 to 24.6 +/- 5.0 at 1.5 T and from 20.5 +/- 5.9 to 47.8 +/- 15.7 at 3 T depending on the timepoint postcontrast.
  
  
  CONCLUSIONS
  Consistently greater tumor enhancement was noted at all measured timepoints following contrast injection with gadobutrol compared to both gadopentetate dimeglumine and gadoterate meglumine at 1.5 T. A substantial further improvement in tumor enhancement was noted using gadobutrol at 3 T.
authors.affiliation: Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany. ulrike.attenberger@medma.uni-heidelberg.de
authors.forename: Ulrike I
authors.initials: UI
authors.lastname: Attenberger
authors.forename: Val M
authors.initials: VM
authors.lastname: Runge
authors.forename: John N
authors.initials: JN
authors.lastname: Morelli
authors.forename: Jonathan
authors.initials: J
authors.lastname: Williams
authors.forename: Carney B
authors.initials: CB
authors.lastname: Jackson
authors.forename: Henrik J
authors.initials: HJ
authors.lastname: Michaely
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis*; D045744:Cell Line, Tumor; D002614:Chelating Agents; D004195:Disease Models, Animal; D019786:Gadolinium DTPA; D005910:Glioma / Q000175:diagnosis*; D006801:Humans; D007477:Ions; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008536:Meglumine; D009942:Organometallic Compounds; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002614:Chelating Agents; D007477:Ions; D009942:Organometallic Compounds; C090600:gadobutrol; D008536:Meglumine; D019786:Gadolinium DTPA; C072417:gadoterate meglumine