Physical Properties of Eu²⁺‐Containing Cryptates as Contrast Agents for Ultrahigh‐Field Magnetic Resonance Imaging

Abstract

The kinetic stabilities and relaxivities of a series of Eu2+-containing cryptates have been investigated. Transmetallation studies that monitored the change in the longitudinal relaxation rate of water protons in the presence of Ca2+, Mg2+, and Zn2+ demonstrated that cryptate structure influences stability, and two of the cryptates studied were inert to transmetallation in the presence of these endogenous ions. The efficacy of these cryptates was determined at different magnetic field strengths, temperatures, and pH values. Cryptate relaxivity was found to be higher at ultra-high field strengths (7 and 9.4 T) relative to clinically relevant field strengths (1.4 and 3 T), but the efficiency of these cryptates decreased as temperature increased. In addition, variation in pH did not yield significant changes in the efficacy of the cryptates. These studies establish a foundation of important properties that are necessary to develop effective positive contrast agents for magnetic resonance imaging from Eu2+-containing cryptates.

Structural Features of Europium(II)‐Containing Cryptates That Influence Relaxivity

“…This influence, albeit limited, of the electronic relaxation time on relaxivity might explain the small bump near 7 T, observable in NMRD profiles of 1 – 3 . The X-band EPR spectra of 1 – 3 were recorded at 110 K. [18] The X-band (0.34 T) line width (Δ H pp , G) values show a slight increase from 1 to 3 , reflecting small difference in their electronic relaxation times. From the bandwidth, the T 2e values were calculated (Table 1), using simplifications introduced by Reuben and adapted by Merbach.…”

Electrochemistry and Spectroelectrochemistry of Luminescent Europium Complexes

“…Literature suggests that Eu(II) does fluoresce in a range of 390 nm to 580 nm, where the emission wavelength shows significant dependence on environment [33][34][35]. It is also possible that the 450 nm band is due to enhanced ligand phosphorescence, which has been seen in some Gd complexes with bpy derivatives [31].…”

Redox‐ and Hypoxia‐Responsive MRI Contrast Agents

“…Modification of 10 yielded a series of Eu 2+ cryptates, the relaxivity of which slightly increases with increasing field strength (4.39 mM −1 s −1 at 1.4 T and 4.80 mM −1 s −1 at 11.7 T at 37 °C for Eu 2+ - 12 ). [46–48] The potential use of Eu 2+ complexes as probes sensitive to pO 2 has been proposed, but none of the aforementioned complexes have been tested in vivo, likely because the necessary oxidative stability of the Eu 2+ state has not yet been fully achieved. [49] …”