Polymeric gadolinium complexes

Polymeric gadolinium chelates are a class of contrast media characterized by their large size. This property is responsible for the fact that leakage into the interstitial space through the normal endothelium lining of the vascular system is either slow or absent, which allows for long imaging windows. Various polymeric agents (e.g. dextrans and polylysine derivatives) with molecular weights ranging from 15,000 to several million Daltons have been evaluated.

Because of their large molecular size, polymeric chelates rotate more slowly. Therefore the rotational correlation time is longer compared to small molecular-weight Gd contrast agents. This, in turn, results in an increased relaxivity of ~16 l/mmol•s or higher at clinical field strengths.

Excretion of Gd-based macromolecular contrast agents is related to the size of the molecule. Since the molecular weight of these large molecules exceeds 40 kD, glomerular filtration decreases which could lead to problems with their excretion. However, these agents are excellent MRA enhancers. Like other types of blood pool agents, they may also be helpful in evaluating the integrity of capillary membranes, for instance in the detection of slow bleeding.

An example of this class of contrast agents is Gadomer (Schering AG, Berlin, Germany), which carries 24 gadolinium atoms. Because of their size (apparent molecular weight 35 kD) Gadomer molecules are large enough to exhibit much slower leakage through normally functioning endothelium than extracellular agents, but are still small enough to be eliminated via the kidneys, by the process of glomerular filtration. Imaging studies in animals have demonstrated the beneficial properties of this dendrimer. A dose of ~25–50 μmol Gd/kg resulted in excellent angiograms and the agent has shown to be suitable for quantitative perfusion studies of the myocardium. Gadomer has also been successfully employed to demonstrate differences in endothelial permeability between tumors and healthy tissue.

None of the polymeric gadolinium complex contrast media are currently commercially available.