MRI Contrast Agents

This introduction highlights the importance of nanomaterials in biomedical applications. The use of different nanosystems in the medical field has conducted researchers to develop numerous synthetic ways.

The magnetic properties of a material are the basis of their applications. Specifically, the contrast agents that will be developed in Chaps. 4 and 5 use their magnetic properties to play their role in magnetic resonance imaging. It is thus important to describe briefly the different magnetisms.

This chapter briefly describes the principle of nuclear magnetic resonance (NMR) and more particularly of magnetic resonance imaging (MRI). This is necessary to fully understand the importance of developing new MRI contrast agents.

The mechanism of action of the paramagnetic gadolinium complexes is briefly described, with an emphasis on the different parameters that can be tuned to increase their efficiency. An overview of the different classes of paramagnetic gadolinium chelates is then presented.

Thanks to their unique properties, inorganic nanostructures have become the center of modern material science. Among existing nanomaterials, magnetic iron oxide nanoparticles (IONP) have attracted a lot of interest. These nanoparticles are suitable for many technological applications such as contrast agent for magnetic resonance imaging. When comparing to molecular MRI probes (Gd-based organic complexes), IONP present many advantages such as a better sensitivity, a poor toxicity, and the possibility to easily modify their surface to develop some properties as multimodality, modulable half-life or specificity. However, one must stress that these properties are related to IONP’s composition, shape and stability (physical and chemical). In that paper, we will introduce some concepts related to IONP’s physico-chemical properties, the synthetic ways to obtain such structures and we will finish with some concepts governing their stability and surface modification.

MRI contrast agents are known for about 30 years. Most of clinical compounds are extracellular agents without tissue specificity. They are excreted by the kidneys (Gd-DTPA, Gd-DOTA, Gd-DTPA-BMA or Gd-HP-DO3A for example). More recently, intracellular agents (Gd-EOB-DTPA, Gd-BOPTA, … undergoing hepatocyte uptake), and blood pool contrast agent (MS-325, binding albumin) have been developed. These Gd complexes have an extended clearance time and allow longer contrast-enhanced imaging sessions. These systems are called “T₁ or positive” agents because they increase the water signal of the tissue areas where they are concentrated. A second kind of contrast agents is made of superparamagnetic iron oxide nanoparticles (USPIO or SPIO). These nanosystems have a high efficiency and are generally “T₂ or negative” agents, inducing a darkening of the region where they accumulate. Such nanoparticles with a diameter of approximately 20–200 nm can be used as contrast agents for liver, lymphatic system (because of macrophage uptake, mainly as negative agent), or blood vessels (because of low extravasation, mainly as positive agent). The different kinds of mechanisms through which they affect the nuclear magnetic relaxation time of the water are briefly described. Nowadays, researches are focused on the development of molecular imaging contrast agents, to target receptors which are overexpressed in pathologies.