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.

Gadolinium(III)-Chelated Silica Nanospheres Integrating Chemotherapy and Photothermal Therapy for Cancer Treatment and Magnetic Resonance Imaging

“…In addition, the large special surface area of silica shell, providing plenty of nano-pores, would possibly allow easy transport of water across the shell and access to the Gd (III) in the core, 34 which may contribute to enhanced T 1 -weighted contrast. 39 Because the silanol groups on the surface will be deprotonated 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 incorporation of ICG into Gd@SiO 2 -DOX/ICG NPs, the surface is coated by PDC which changes the surface charges from -11.9 mV to the positive 48.1 mV. Detailed information about the surface properties and the color during the preparation and durg loading is shown in Table S3 and Figure S4.…”

Metal Complexes as MRI Contrast Enhancement Agents

“…Several examples of comparison between structurally similar, but differently charged, complexes have been reported. 16,64,79,87 The water-exchange rate is hardly affected by substituents that do not directly interfere in the inner coordination sphere. Different bisamide DTPA derivatives have similar Scheme 2 Ligands resulting in increased steric crowding around the Gd 3+ ion.…”

“…Several factors should be considered to rationalize these differences between the eight-coordinate aqua ion and the ninecoordinate complexes. 35,79 The rate constant and the mechanism of water exchange are closely related to the inner-sphere solution structure of the complexes. In [Gd(H 2 O) 8 ] 3+ , the rearrangement of the flexible eight-coordinate inner sphere to reach the ninecoordinate transition state is easy.…”

Matrix-Assisted Ionization-Ion Mobility Spectrometry-Mass Spectrometry: Selective Analysis of a Europium–PEG Complex in a Crude Mixture

“…The prevalent use of magnetic resonance imaging (MRI) as a tool in clinical medicine and biomedical research is a result of the useful features of the technique, including its noninvasive nature [49][50][51][52]. Recently, a europium based poly(ethylene glycol) (PEG) 2-arm conjugate (Eu-PEG) was synthesized to study fundamental properties relating to contrast agent performance [52,53] but the analyses of Eu-PEG complex (net charge +1) was difficult.…”

“…Recently, a europium based poly(ethylene glycol) (PEG) 2-arm conjugate (Eu-PEG) was synthesized to study fundamental properties relating to contrast agent performance [52,53] but the analyses of Eu-PEG complex (net charge +1) was difficult. Here, we use this crude sample exemplifying the intricate nature of standard polymer characterization methods and demonstrate the unique ionization and separation abilities of MAI-IMS-MS for Eu-PEG complexes directly from the crude sample.…”