EuII-containing cryptates as contrast agents for ultra-high field strength magnetic resonance imaging

Abstract

The relaxivity (contrast-enhancing ability) of EuII-containing cryptates was found to be better than a clinically approved GdIII-based agent at 7 T. These cryptates are among a few examples of paramagnetic substances that show an increase in longitudinal relaxivity, r1, at ultra-high field strength relative to lower field strengths.

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

“…The slopes of the lines afford relaxivities (2.1 and 3.7 mM −1 s −1 for complexes 1 and 2 , respectively) that match reported values. [9] These values are also consistent with the relaxivities expected for low molecular weight chelates. Because the data in Figure 3 can be well-described by one line, it is unlikely that complexes 1 and 2 aggregate at concentrations below 10 mM.…”

“…Below 3.8 mM, a linear relationship was observed with a relaxivity value of 4.3 mM −1 s −1 , expected for complex 3 . [9] A change in the slope of the line was observed above 3.8 mM, consistent with a higher relaxivity value of 12.1 mM −1 s −1 . This change in slope is likely due to the formation of aggregates occurring through intermolecular hydrophobic interactions between biphenyl moieties.…”

Oxidation-responsive Eu2+/3+-liposomal contrast agent for dual-mode magnetic resonance imaging

“…The observation of T 1 changing upon air exposure is in good agreement with the T 1 -shortening nature of Eu(2.2.2) 2+ (relaxivity was 3.99 mM −1 s −1 outside of liposomes and 0.2 mM −1 s −1 inside of liposomes at 20 °C and 11.7 T. The lower relaxivity is expected for T 1 -shortening contrast agents encapsulated in spherical liposomes). 21,26 Furthermore, the change in T 1 upon air exposure indicates that oxidation to form Eu(2.2.2) 3+ caused the observed lengthening of T 1 .…”

“…Furthermore, Eu 2+ has a tunable oxidation potential 20 and outperforms clinically approved T 1 -shortening contrast agents at ultra-high magnetic field strengths. 21 To address the need for a concentration-independent, oxidation-responsive contrast agent, we hypothesized that encapsulating the Eu 2+ -containing complex (4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane europium(II), Eu(2.2.2) 2+ , Fig. 1) in liposomes would produce an oxidation-responsive dual-mode contrast agent because it would enhance either T 1 -weighted images or CEST images depending on the oxidation state of Eu.…”

A (Fluoroalkyl)Guanidine Modulates the Relaxivity of a Phosphonate-Containing T 1 -Shortening Contrast Agent

“…[25] To obtain τ m −1 , NMR linewidth at half height of the 17 O-labelled bulk water peak obtained from 1% 17 O-enriched aqueous solutions of Y-DOTP 5− and Gd-DOTP 5− are fitted to Swift and Connick equation. [26] The water exchange rates obtained for GdDOTP 5− and Gd-DOTA − systems are listed in Tables 2 and 3, respectively. For Gd-DOTP 5− system, adding 4 equiv.…”