Metal ion release from paramagnetic chelates: What is tolerable?

Abstract

At the currently administered clinical doses, paramagnetic metal chelate complexes presently used as MR contrast enhancement agents appear to be relatively nontoxic. Solution thermodynamic, solubility, and selectivity studies, based on a number of gadolinium chelate complexes, indicate that very little gadolinium is released in vivo, and the small amounts that do remain are available for excretion, albeit slowly. Although the mechanism of metal release from manganese-based chelate complexes is not well understood, any released manganese is likely to be quickly and efficiently cleared through the liver. Although MRI contrast agents are unlikely to be administered repeatedly in patients, which could result in accumulation of metal ion, the long-term effects of such potential deposition have yet to be demonstrated.

Relaxometric Study of Copper [15]Metallacrown‐5 Gadolinium Complexes Derived from α‐Aminohydroxamic Acids

“…This is a necessary condition for their possible use as MRI contrast agents, because small amounts of ligand, free copper(ii) ions, or free gadolinium(iii) ions would be toxic. [11] The CHN elemental analysis results are given in the Experimental Section.…”

Utilization of Electron Probe Microanalysis in Gadolinium-Treated Mice

“…The suitability of a gadolinium complex as an imaging contrast agent is dependent upon the presence of ligands that have high affinity for gadolinium, thereby yielding highly stable and nontoxic gadolinium complexes in vivo (3,20). Metal chelates of gadolinium are used to eliminate the toxicity posed by free gadolinium (3,6,7).…”

1H T1 and T2 measurements of the MR imaging contrast agents Gd-DTPA and Gd-DTPA BMA at 1.5T

“…This reduces the osmolality of the injected solution as well as the stability constant. Although the thermodynamic stability constant of Gd-DTPA BMA at pH 11 is nearly six orders of magnitude smaller compared with Gd-DTPA, it is still remarkably stable (log K = 16.9) [12]. Furthermore, stable nonionic paramagnetic metal ion chelates have, in general, the advantage of being well and even better tolerated compared with their ionic counterparts.…”