Strategies for optimizing water-exchange rates of lanthanide-based contrast agents for magnetic resonance imaging

Abstract

This review describes recent advances in strategies for tuning the water-exchange rates of contrast agents for magnetic resonance imaging (MRI). Water-exchange rates play a critical role in determining the efficiency of contrast agents; consequently, optimization of water-exchange rates, among other parameters, is necessary to achieve high efficiencies. This need has resulted in extensive research efforts to modulate water-exchange rates by chemically altering the coordination environments of the metal complexes that function as contrast agents. The focus of this review is coordination-chemistry-based strategies used to tune the water-exchange rates of lanthanide(III)-based contrast agents for MRI. Emphasis will be given to results published in the 21st century, as well as implications of these strategies on the design of contrast agents.

Figure 1

Optimum water-exchange rates of T₁ and PARACEST agents.

Figure 2

Representative Gd^III-containing complexes that undergo water exchange via dissociative (1 and 2), dissociative interchange (9), associative (3, 4, 7, 8, 10, and 11), and associative interchange (5 and 6) processes [28,29,30,31,32,33,34,35,36,37].

Figure 3

Ground and transition states of the water-exchange process. A. Stabilization and destabilization of the ground state lead to slower and faster water exchange-rates, respectively. B. Stabilization and destabilization of the transition state lead to faster and slower water-exchange rates, respectively.

Figure 4

Representative Gd^III- and Eu^III-containing complexes that relate the influence of charge (compounds 12–26) and electron density of coordinating atoms (compounds 27–42) to water-exchange rate [38,39,40,41,42,43,44,45,46,47,48,49].

Figure 5

Representative Gd^III-containing complexes 43–65 that relate the influence of steric hindrance at the water-coordination site to water-exchange rate [10,50,51,52,53,54,55,56,57,58,59,60,61,62].

Figure 6

Coordination polyhedron of Gd^III-containing complex 43 [10].

Figure 7

Representative complexes 66–87 that relate the influence of bulkiness and polarity of ligand side chains and water-exchange rates [15,27,63,64,65,66,67,68,69].

Figure 8

Representative complexes 88–97 that relate the influence of TSAP/SAP ratios with water-exchange rates of DOTA-type complexes [41,71,72,73,74,75,76,77,78].

Figure 9

Top-down view of (left) TSAP and (right) SAP isomers with the O–Gd^III–N twist angles indicated. In these views, the oxygen plane is above the Gd^III ion and the nitrogen plane is below the Gd^III ion.