Relaxivity of Gadolinium(III) Complexes: Theory and Mechanism

Abstract

The aim of using a contrast agent in Magnetic Resonance Imaging is to accelerate the relaxation of water protons in the surrounding tissue. This objective can be achieved by paramagnetic substances. In 1948, Bloch et al. reported the use of the paramagnetic ferric nitrate salt to enhance the relaxation rates of water protons [1]. Some 30 years later, Lauterbur et al. applied a Mn(II) salt to distinguish between different tissues based on the differential relaxation times and thus produced the first MR image [2]. Nowadays, Gd(III) complexes are far the most widely used MRI contrast agents in the clinical practice. The choice of Gd(III) is explained by its seven unpaired electrons which makes it the most paramagnetic stable metal ion. Beside this, Gd(III) has another significant feature: owing to the symmetric S-state, its electronic relaxation is relatively slow which is relevant to its efficiency as an MRI contrast agent.As most of the current contrast agent applications in MRI concerns Gd(III) complexes, this chapter will focus on the discussion of relaxation theory and the experimental results on Gd(III)-based agents. Several reviews have been published on this topic [3][4][5][6][7]. In addition to Gd(III) compounds, a Mn(II) chelate, Mn(II)DPDP, is the only metal complex which has been approved as an MRI contrast agent (DPDP = N,N -dipyridoxylethylenediamine-N,N -diacetate 5,5 -bis(phosphate)) [8]. Mn(II)DPDP is a weak chelate that dissociates in vivo to give free manganese which is taken up by hepatocytes [9]. The presence of the ligand is necessary because it facilitates a slower release of manganese than would have been the case had manganese been administered as a simple salt, such as manganese chloride.

Innovative Design of Ca-Sensitive Paramagnetic Liposomes Results in an Unprecedented Increase in Longitudinal Relaxivity

“…Furthermore, only the data measured at the intermediate-to-high fields (Larmor frequency >4 MHz) were considered in the fitting procedure due to the well-known limitations of the SBM theory to accurately describe the low field relaxivity for slowly tumbling systems. 14 The NMRD data were nicely fitted by the relaxation model developed ( Figure 5 and Table 4). The values of the empirical parameters that are commonly used to describe the electronic relaxation of Gd(III) (i.e., Δ 2 and τ V ) are fully consistent with the numbers typically reported for slowly tumbling macrocyclic Gd-chelates.…”

Optimizing the high-field relaxivity by self-assembling of macrocyclic Gd(iii) complexes

“…paramagnetic centre. 17 The decrease of τ M for YL 1 -GdL 2 , from 1.6 to 0.3 µs at 25°C, is particularly evident and might be attributed to two reasons: 1) the decrease in the positive charge upon the binding to an alkylphosphonate group; 2) steric compression of the phosphonate group at the water binding site that destabilises the nine-coordinate ground state in the dissociative exchange mechanism. 18 In the case of YL 2 -GdL 1 , it is probable that only steric effects are operative and so the change in τ M is less pronounced (from 1.4 to 0.8 µs).…”

“…This behaviour is well understood: we are observing a change in the hydration number from q = 2 to 0 during this change in pH that is a consequence of the formation of a ternary complex with the carbonate present in the basic aqueous solution. 14 The rate of water exchange of the complex has been determined, at pH=6.5, by measuring the temperature dependence of the transverse relaxation rate (R 2 = 1/T 2 ) of the solvent using 17 O NMR at 2.1 T (Fig. 3, left).…”

“…The relaxometric characterisation will separate the contributions of the two constituent parts and characterise the effect that the binding has had on each gadolinium centre at a time. This will be done by making one part of the dimeric self-recognition complex diamagnetic, by using Y(III) instead of Gd(III), characterising by 1 H and 17 O relaxation rate measurements, and then swapping the diamagnetic and paramagnetic moieties and repeating the characterisation. In this way, it is possible to study the effect of the binding interaction on each monomer separately from the other as only the paramagnetic half will be "seen" by the instrumentation.…”

“…Figure 5. Plot of the temperature dependence of the transverse 17 O relaxation rate of YL 1 -GdL 2 (7 mM; red diamonds) and YL 2 -GdL 1 (9 mM; blue circles) at 2.1 T.…”