ABSTRACT

In that context, many nanostructures have been developed in the past decades to (i) increase MRI sensitivity while keeping a positive contrast enhancement to get quantitative results more easily, and (ii) tune the biodistribution of the contrast agent for tissue-targeting purpose. Moreover, these nanostructures can often support additional attractive features to combine imaging and therapeutic functionalities and/or to induce a contrast in different complementary imaging techniques (optical, MRI, positron emission tomography (PET), ultrasound, etc.). This chapter will focus specifically on the different nanostruc-tures-based strategies employed to increase the sensitivity and specificity of the positive contrast agents. To increase the sensitivity of rare earth based contrast agents, three parameters are usually considered: (i) increasing the number of Gd per contrast agent, (ii) increasing the rotational correlation time by increasing molecular weight and size, and (iii) increasing the number of coordinated water molecules. The sensitivity of a given contrast agent is classically quantified by measurements of the longitudinal and transverse relaxivity values, r1 and r2, which refer to the amount of increase in 1/T1and 1/T2, respectively, per millimolar of agent (often given as per mM of Gd). The ratio r2/r1 is used to classify the contrast agent as positive T1 agents, which usually have r2/r1 ratios of 1-2, or as negative T2 agents, which have r2/r1 ratios as high as 10 or more. For nanostructure elements, it is not only the relaxivity per Gd that defines the efficiency of the contrast agent but also the number of Gd per nanomaterial. It is then of interest to compute the relaxivity values per mM of nanomaterial, instead of per mM of Gd. The first part of this chapter is dedicated to a review of different strategies to confer the ability to enhance the contrast of magnetic resonance images by grafting gadolinium chelates to various nanoparticles, while the second part is devoted to the development of rare earth elements containing crystalline nanoparticles (Scheme 4.2). It must be pointed out that the topic of this chapter is limited to “solid” nanoparticles, although a large range of vesicles, liposomes, and micelles have been successfully developed as contrast agents for MRI. Moreover, only a few examples of other rare earth elements (Dy, Ho), even if they exhibit an interesting potential for the design of particulate contrast agent for MRI, are given in this chapter since the data are rather rare as compared to particulate contrast agent

based on gadolinium. This chapter will also introduce the use of such magnetic resonance contrast agents for both imaging and therapy in the final section.