Gadolinium complex

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. 

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Future Applications. The use of gadolinium complexes as contrast agents in magnetic resonance imaging (mri) is growing (40). 

Kinetics of dissociation of one yttrium and seven gadolinium complexes of polyazaphosphinic acid ligands, 9 with the four CH2PO ... 

The gadolinium complex GdHPDOSA can be trapped inside the interior of apoferritin (60). The process is based on the dissociation of the apoprotein into subunits at low pH in a concentrated solution of the complex followed by its reforming at pH 7. The complex molecules that are not trapped inside the protein are eliminated by dialysis. The longitudinal relaxivity of the... 

Several types of particulate compounds have been studied so far. Among these are solid nanoparticles containing gadolinium complexes 98) or macro-molecular systems such as polylysine 99). 

Both ligands are amides of DTPA and are obtained by treating the dianhydride of DTPA with the corresponding amine (methyl amine [15] and methoxyethylamine [16] respectively). These gadolinium complexes are freely soluble in water. As expected, the osmolality of the 0.5 molar solution of gadodiamide is lower (0.79 osmol/kg water) than that of the 0.5 molar solution of Gd-DTPA (gadopentetate) (Table 2) [17,18]. 

Table 2. Physico-chemical properties of formulations of gadolinium complexes...

A second class of MRI contrast agents contains ligands that are derivatives of the macrocydic tetramine, 1.4.7.10-tetraazacyclododecane (cyclen). Gadoterate (Dotarem, Gd-DOTA, Scheme 3, formula 5) was the first macrocydic gadolinium complex which has entered the market. 

Neutral bis-and tris-gadolinium complexes of the oligomeric ligands have been obtained in the usual manner with gadolinium oxide and the corresponding dysprosium complexes by reaction with dysprosium oxide The latter might be useful as X-ray contrast agents. 

The protein binding of compounds with such low partition coefficients is virtually non-existent as demonstrated by MRI and pharmacokinetic studies. The low protein binding of the extracellular gadolinium complexes currently used in clinical practice correlates very well with their excellent safety profile. 

Standard formulations of the extracellular gadolinium complexes have a concentration of 0.5 mol/1. Gadobutrol and gadoteridol can be formulated even as 1.0-molar solutions with acceptable viscosity (Table 2). 

In this procedure the pentameglumine salt of the ligand DTPA was added to prevent any undesired release of the gadolinium ion from the chelate. Gadolinium-complex formulations normally contain a small amount of excess ligand either in its free or calcium-complexed form. As mentioned above, Pro-Hance (gadoteridol) contains calteridol, the calcium salt of the relatively weak calcium complex of the ligand for instance. 

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]. 

Pharmacokinetic results in humans have confirmed the favourable findings in animal studies. Thus the clinical use of extracellular gadolinium complexes as diagnostic tools in MRI has become routine practice in many fields of interest among others for diagnosing tumours, infections, inflammations and infarctions particularly in the Central Nervous System (CNS). 

The combination of advanced imaging techniques tailored to the optimal efficacy of the extracellular gadolinium complexes will further improve the diagnostic potential of MRI in the future. 

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