Dissociation Kinetics of Open‐Chain and Macrocyclic Gadolinium(III)‐Aminopolycarboxylate Complexes Related to Magnetic Resonance Imaging: Catalytic Effect of Endogenous Ligands

Abstract

The kinetics of the metal exchange reactions between open-chain Gd(DTPA)(2-) and Gd(DTPA-BMA), macrocyclic Gd(DOTA)(-) and Gd(HP-DO3A) complexes, and Cu(2+) ions were investigated in the presence of endogenous citrate, phosphate, carbonate and histidinate ligands in the pH range 6-8 in NaCl (0.15 M) at 25 °C. The rates of the exchange reactions of Gd(DTPA)(2-) and Gd(DTPA-BMA) are independent of the Cu(2+) concentration in the presence of citrate and the reactions occur via the dissociation of Gd(3+) complexes catalyzed by the citrate ions. The HCO(3)(-)/CO(3)(2-) and H(2)PO(4)(-) ions also catalyze the dissociation of complexes. The rates of the dissociation of Gd(DTPA-BMA), catalyzed by the endogenous ligands, are about two orders of magnitude higher than those of the Gd(DTPA)(2-). In fact near to physiological conditions the bicarbonate and carbonate ions show the largest catalytic effect, that significantly increase the dissociation rate of Gd(DTPA-BMA) and make the higher pH values (when the carbonate ion concentration is higher) a risk-factor for the dissociation of complexes in body fluids. The exchange reactions of Gd(DOTA)(-) and Gd(HP-DO3A) with Cu(2+) occur through the proton assisted dissociation of complexes in the pH range 3.5-5 and the endogenous ligands do not affect the dissociation rates of complexes. More insights into the interaction scheme between Gd(DTPA-BMA) and Gd(DTPA)(2-) and endogenous ligands have been obtained by acquiring the (13)C NMR spectra of the corresponding diamagnetic Y(III)-complexes, indicating the increase of the rates of the intramolecular rearrangements in the presence of carbonate and citrate ions. The herein reported results may have implications in the understanding of the etiology of nephrogenic systemic fibrosis, a rare disease that has been associated to the administration of Gd-containing agents to patients with impaired renal function.

Coupling Fast Water Exchange to Slow Molecular Tumbling in Gd3+ Chelates: Why Faster Is Not Always Better

“…The Gd 3+ chelates of DOTA and its derivatives are more thermodynamically stable and more kinetically robust than their DTPA counterparts. 22 They are more suitable for applications that require prolonged in vivo lifetimes, and controversy surrounds the isolated cases in which GdDOTA has been associated cases of NSF. 23 In general, DOTA derivatives are considered sufficiently stable for prolonged in vivo residence lifetimes, and therefore for targeted applications.…”

Cationic gadolinium chelate for magnetic resonance imaging of cartilaginous defects

“…partly contribute to this dissociation. (23) No transmetallation was detected in samples containing Gd-DOTA or Gd-DOTA-Am4 over the course of 72 hours. Therefore, it can be concluded that Gd-DOTA-Am4 is significantly more stable than Gd-DTPA.…”

Fibrosis sistémica nefrogénica: la pandemia que no fue

“…Por ejemplo, gadodiamida tiene una vida media de 2 h en individuos sanos con función renal normal y aumenta a alrededor de 30 h en pacientes con ERC etapa 5 36 . El gadolinio libre puede unirse a aniones disponibles en el medio como fosfato, formando sales insolubles y depositándose en los tejidos 37 . Se ha detectado depósitos de gadolinio en biopsias de piel 38,39 y otros tejidos de pacientes con FSN 40,41 , pero no en la piel de individuos sanos expuestos a MC basados en gadolinio 42 .…”