Chemistry of Gadolinium Based Contrast Agents

Gd complexes of MRI CAs have contributed significantly to lanthanide chemistry. In the past two decades, scientists have designed a vast number of complexes to improve the relaxiv-ity and selectivity of CAs. Understanding the chemistry of CAs not only gives information about the pharmacological properties of these substances, but also forms the basis for their improvement. 

nearly half of all MR examinations are contrast enhanced. CAs are a distinctive class of pharmaceuticals, in that they are applied to improve the contrast between normal and diseased tissues, or at the site of interest, but are not intended to cause unnecessary biological activity. The development of MRI CAs from bench to patient is a multi-step process that can take more than 10 years [5]. 

The motion of the protons in the proximity of Gd-based CAs contributes to the relaxivity, which is defined as the relaxation rate at a 1 mM concentration. Paramagnetic compounds, such as Gd complexes, increase the 1/Ti and I/T2 of solvent nuclei. The observed relaxivity (l/TlOobs is composed of the diamagnetic relaxation (1/U)d and the paramagnetic relaxation (l/TOp, which refer to the solvent relaxation in the absence and presence of paramagnetic compounds, respectively, as shown in Equation 10.1. 

Interactions of water protons account for an alteration of the local magnetic field surrounding a paramagnetic center. The observed relaxivity depends on the distance and time of these interactions and the translational diffusion. The interactions are classified as either inner-sphere, which describes protons of water molecules that are bound to the metal center, or outer-sphere, which describes bulk solvent molecules that experience a paramagnetic effect when they diffuse around the metal center. The diamagnetic contribution has a linear relationship 

The inner-sphere relaxation refers to the contribution from the water molecules that are directly bound to the gadolinium, and is expressed by the Solomon-Bloembergen equations (Equations 10.3-10.6) [15, 16], 

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