Can gadolinium III [Gd(III)] complexes be considered good candidates for magnetic resonance (MR)‐molecular imaging studies? In this review article, we examine the principal issues that are the basis of successful use of Gd‐based protocols in molecular imaging applications. High relaxivity is the primary requisite. Therefore, the design of such paramagnetic probes has to be pursued keeping in mind the relationships between structure, dynamics, and the relevant parameters involved in paramagnetic relaxation processes. Moreover, the limited number of target molecules on cellular membranes makes it necessary to define strategies aimed at delivering many Gd‐containing moieties to the sites of interest. Examples are reported for the attainment of very high relaxivities for the design of new routes for pursuing the accumulation of small sized Gd(III) complexes at the targeting sites. An efficient cellular uptake of Gd‐containing probes is the key step for attaining the visualization of targeted cells by MR imaging, and selected examples are reported. In this context, the problem of the assessment of the minimum amount of Gd(III) complexes necessary for the MR imaging‐visualization of cells has been addressed by reporting the authors' observations on the cell‐internalization of Gd(III) complexes. A particularly efficient delivery system is represented by Gd‐loaded apoferritin, which allows the MR visualization of hepatocytes when the number of Gd‐complexes per cell is 4 ± 1 × 10⁷. Finally, the potential of responsive systems is considered by outlining the exploitation of the amplification effect brought about by the action of a specific enzymatic activity on the relaxivity of a suitably functionalized Gd(III) complex. J. Magn. Reson. Imaging 2002;16:394–406.

This article presents a facile strategy to combine Eu³⁺ and Gd³⁺ ions into coacervate core micelles in a controlled way with a statistical distribution of the ions. Consequently, the formed micelles show a high tunability between luminescence and relaxivity. These highly stable micelles present great potential for new materials, e.g. as bimodal imaging probes.

Cyclic hexapeptoids are able to efficiently bind Gd³⁺ions. Their thermodynamic stabilities have been assessed by¹H-relaxometric investigations.

Poly-aromatic peptide sequences are able to self-assemble into a variety of supramolecular aggregates such as fibers, hydrogels, and tree-like multi-branched nanostructures. Due to their biocompatible nature, these peptide nanostructures have been proposed for several applications in biology and nanomedicine (tissue engineering, drug delivery, bioimaging, and fabrication of biosensors). Here we report the synthesis, the structural characterization and the relaxometric behavior of two novel supramolecular diagnostic agents for magnetic resonance imaging (MRI) technique. These diagnostic agents are obtained for self-assembly of DTPA(Gd)-PEG8-(FY)3 or DOTA(Gd)-PEG8-(FY)3 peptide conjugates, in which the Gd-complexes are linked at the N-terminus of the PEG8-(FY)3 polymer peptide. This latter was previously found able to form self-supporting and stable soft hydrogels at a concentration of 1.0% wt. Analogously, also DTPA(Gd)-PEG8-(FY)3 and DOTA(Gd)-PEG8-(FY)3 exhibit the trend to gelificate at the same range of concentration. Moreover, the structural characterization points out that peptide (FY)3 moiety keeps its capability to arrange into β-sheet structures with an antiparallel orientation of the β-strands. The high relaxivity value of these nanostructures (~12 mM⁻¹·s⁻¹ at 20 MHz) and the very low in vitro cytotoxicity suggest their potential application as supramolecular diagnostic agents for MRI.