Gd retention in the body

Gadolinium-based contrast agents (GBCAs) are commonly used in clinical settings as they add physiological information to the superb anatomical information of MR images. Millions of Contrast Enhanced-MRI scans have been acquired in the past three decades without reporting clinical evidence for frequent serious acute or chronic events. Hence, GBCAs are considered to be among the safest parenteral chemicals.
However, recently, several studies have shown the occurrence of an increased signal intensity in non-enhanced T1-weighted MRI of some brain regions in patients with normal renal function who had previously received multiple doses of GBCAs. The observed hyperintense signal has been associated with the retention of small amounts of gadolinium (Gd) in the brain. There has been evidence that both linear and macrocyclic GBCAs can yield detectable Gd traces in the brain, with linear neutral agents leaving greater quantities. The intrinsic difficulties associated with the availability of human biopsies prompted the development of animal models to investigate Gd-retention in the brain. It has been found that successive administrations of GBCA to rodents over periods of few weeks lead to the retention of Gd in the brain structures that mimic the pattern observed in patients.

At CIM the following research area are currently developed:

  • Evaluation of the speciation of Gd-containing species after multiple administrations GBCAs through the quantification of the amount of intact Gd-complexes and insoluble Gd-containing species.
  • Investigation of the role of the thermodynamic and kinetic stability of the Gd-complexes on the extent of their retention in vivo.
  • Extension of the investigation of Gd retention to other body tissues besides brain in order to get a comprehensive view which can help in the understanding of Gd accumulation/excretion pathways.
  • Investigation of the distribution and speciation of GBCAs in the different blood components (Red Blood Cells, Leukocytes and serum).

Group Leaders:

Eliana Gianolio