title: Brain tumor enhancement in magnetic resonance imaging: dependency on the level of protein binding of applied contrast agents.
abstract: OBJECTIVE
  To evaluate the dependency of tumor contrast enhancement (CE) in regard to protein-binding properties of contrast agents, using 4 different agents with a wide range of protein-binding capacities in a standardized rat brain glioma model.
  
  
  METHODS
  Sixteen rats with implanted brain gliomas were evaluated at 1.5 T with a multielement wrist coil in 2 different comparative settings. In both groups, a non-protein-binding agent (gadopentetate dimeglumine, Bayer Healthcare Inc.) and a weak protein-binding agent (gadobenate dimeglumine, Bracco Diagnostics Inc.) were applied and compared with either a approximately 90% protein-binding agent (group A; B22956/1, Bracco Research USA) or a approximately 50% protein-binding agent (group B; BRU 52, Bracco Research USA). All agents were applied at a dose of 0.1 mmol/kg and a single data acquisition with standard T1-weighted turbo spin-echo sequence (TR/TE = 480/15 ms) was initiated 10 seconds after injection. Evaluation of tumor CE and contrast-to-noise ratio (CNR) was based on region of interest measurements within the tumor and remote normal brain.
  
  
  RESULTS
  With B22956/1 (group A), CE increased by 93% in comparison with gadobenate dimeglumine (15.0 +/- 5.3 vs. 7.8 +/- 2.7; P = 0.010) and by 136% in comparison with gadopentetate dimeglumine (15.0 +/- 5.3 vs. 6.4 +/- 1.9; P = 0.013). CNR using B22956/1 increased by 116% in comparison with gadobenate dimeglumine (14.0 +/- 5.9 vs. 6.5 +/- 2.6; P = 0.015) and increased by 138% in comparison with gadopentetate dimeglumine (14.0 +/- 5.9 vs. 5.9 +/- 1.7; P = 0.034). Using BRU 52 (group B), CE increased by 60% in comparison with gadobenate dimeglumine (21.7 +/- 1.4 vs. 13.6 +/- 2.5; P = 0.013) and by 94% in comparison with gadopentetate dimeglumine (21.7 +/- 1.4 vs. 11.2 +/- 0.5; P < 0.0001). CNR using BRU 52 increased by 72% in comparison with gadobenate dimeglumine (21.2 +/- 1.3 vs. 12.3 +/- 3.1; P = 0.0002) and by 122% in comparison with gadopentetate dimeglumine (21.3 +/- 1.3 vs. 9.6 +/- 0.8; P < 0.0001).
  
  
  CONCLUSIONS
  The protein-binding capacity of gadolinium chelates shows a significant impact on CE and CNR in brain tumors with disrupted blood-brain barrier. In comparison with currently approved agents, high albumin-binding agents show further improved brain tumor CE. However, the time course of enhancement and optimal time frame for scanning after injection of agents with higher protein-binding capacities (approximately 50%-90%) has yet to be evaluated.
authors.affiliation: Department of Clinical Radiology, University of Munich Hospitals-Grosshadern Campus, Ludwig-Maximilians-University, Munich, Germany. Bernd.Wintersperger@med.uni-muenchen.de
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Wintersperger
authors.forename: Val M
authors.initials: VM
authors.lastname: Runge
authors.forename: Michael F
authors.initials: MF
authors.lastname: Tweedle
authors.forename: Carney B
authors.initials: CB
authors.lastname: Jackson
authors.forename: Maximilian F
authors.initials: MF
authors.lastname: Reiser
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003287:Contrast Media / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011856:Radiographic Image Enhancement / Q000379:methods*; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; D009419:Nerve Tissue Proteins