Gadolinium extracellular chelates

All currently available extracellular contrast agents are gadolinium chelates. This rare earth metal ion exhibits the strongest effect of all elements on the longitudinal relaxation time Tl. The ligands of these chelates belong to two different types of structure Acyclic (open-chain) compounds and macrocyclics. 

Two extracellular contrast agents which contain neutral gadolinium chelates have entered the market gadodiamide (Omniscan) (Fig. 4 a) and gadoverse-tamide (Optimark) (Fig. 4b). 

The development of low osmolar non-ionic X-ray contrast agents has resulted in a distinct reduction in the toxicity and the observed side-effects in patients. However, as already mentioned the osmotic activity of MRI contrast agents is less important in view of the smaller injection volumes which are used. All the formulations of extracellular gadolinium chelates are hypertonic when compared with blood. But the overall increase in osmolality after injection of even 0.3 mmol/kg body weight is insignificant. Osmololatiy-induced adverse reactions have been observed rarely not only because of the relatively small injection volumes but also because of the rapid dilution of the injected agent in the blood. 

The extra-renal excretion of the extracellular gadolinium complexes is negligible and no significant absorption after enteral application has been observed. The elimination half-life depends on the glomerular filtration rate, and on the cardiovascular function. No significant differences between the gadolinium chelates have been observed, their terminal half-lives in blood are in the range of 15 to 75 minutes in animals and 1-2 h in humans [65-67]. 

The pharmacokinetic parameters of the extracellular gadolinium chelates do not exhibit any dose dependency. The analysis of plasma and urine samples gave no evidence for any biotransformation of the compounds [69-71]. 

Gadolinium chelates for MRI (SEDA 18, 446) (SEDA-20, 419) (SEDA-21, 475) (SEDA-22, 503) are inert, non-metabolized, small molecules, with essentially the same pharmacokinetic properties as the iodinated contrast agents. They are rapidly distributed in the extracellular fluid spaces, both intravascular and extravascular, although they do not cross the normal blood-brain barrier, and are almost entirely excreted by glomerular filtration, with no significant active tubular excretion or re-absorption. Hepatic excretion occurs in patients with... 

A variety of liver contrast agents have been developed for contrast-enhanced MR imaging of the liver, which are designed to overcome the limitations of extracellular low molecular gadolinium chelates. The two main classes of liver-specific contrast agents are the superparamagnetic iron oxide (SPIO) with uptake via the reticuloendothelial system (RES) mainly into the liver and spleen, and the hepatobiliary contrast agents with uptake into hepatocytes followed by variable biliary excretion. 

Extracellular contrast agents non-specific gadolinium chelates... 

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