Gadolinium chelates with weak binding to serum proteins. A new class of high-efficiency, general purpose contrast agents for magnetic resonance imaging

Invest Radiol. 1997 Dec;32(12):780-96. doi: 10.1097/00004424-199712000-00009.


Rationale and objectives: The authors assess the effect of weak protein binding on the efficacy of gadolinium chelates as contrast agents for magnetic resonance imaging (MRI).

Methods: Chelates with no (gadopentetate dimeglumine), weak (gadobenate dimeglumine), and strong (B-21326/7) protein binding were compared by in vitro MRI at 2T (spin echo [SE]: repetition time [TR]/echo time [TE] 350/8 mseconds) on solutions in 0.5 mM bovine serum albumin and in rat whole blood, and by in vivo MRI at 2T on rat models of brain tumors (SE TR/TE 350/10 mseconds) and of focal blood-brain barrier disruption (SE TR/TE 400/15 mseconds) after injection of MPP+. Relaxation rate enhancement in the blood of normal rabbits was measured in vivo after administration of contrast agents using IR-Snapshot FLASH.

Results: Signal intensity enhancement measured in vitro for whole rat blood 0.1 mM in gadobenate was 142% relative to the same concentration of gadopentetate. Peak signal intensity enhancement in brain tumors was 87% +/- 8% and 64% +/- 5% after 0.1 mmol/kg intravenous administration of gadobenate and gadopentetate, respectively; in MPP+ lesions, the peak signal intensity enhancement was 22% +/- 9%, 32% +/- 7%, and 64% +/- 14% after 0.2 mmol/kg intravenous of gadopentetate, gadobenate, and B-21326/7, respectively. In rabbits, the relaxation enhancement of blood 5 minutes after B-21326/7 and gadobenate administration was 323% and 182%, respectively, relative to the same dose (0.1 mmol/kg intravenous) of gadopentetate.

Conclusions: Weak protein binding can substantially increase the efficacy of gadolinium chelates as general purpose contrast agents for MRI.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blood Proteins / metabolism*
  • Blood-Brain Barrier / physiology
  • Brain / pathology
  • Brain Neoplasms / blood
  • Brain Neoplasms / diagnosis*
  • Cattle
  • Contrast Media / metabolism*
  • Disease Models, Animal
  • Gadolinium DTPA / metabolism*
  • Image Enhancement / methods
  • Magnetic Resonance Imaging*
  • Meglumine / analogs & derivatives*
  • Meglumine / metabolism
  • Organometallic Compounds / metabolism*
  • Protein Binding
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley


  • Blood Proteins
  • Contrast Media
  • Organometallic Compounds
  • gadobenic acid
  • Meglumine
  • Gadolinium DTPA