Reduction

The limited sensitivity of MRI is the major drawback to the thorough involvement of this modality in Molecular Imaging applications. Therefore the search for high sensitivity agents continues to be an active line of research in probe development laboratories [1] . Several nanocarriers have been considered in order to deliver a sufficient number of contrast agents to the targeting sites and to pursue their visualisation in MR images. For instance Lanza and Wickline reported solid-lipid microemulsions that can be loaded with 10 5 amphiphilic Gd-chelates and allow the detection of targets that are present at hundreds picomolar concentration [2] . Afterwards Mulder and Nicolay reported several successful examples of targeting probes using micelles and liposomes loaded with Gd-complexes bearing lipidic chains [3] . Although, such particles display an excellent sensitivity, some concern exists for their use ”in vivo”, either for the metabolic fate of the amphiphilic Gd-complexes as well as for the macrophages uptake of the circulating particles. Both drawbacks are overcome if the particle consists of endogenous systems such as ferritin and the loaded agent has a well tolerated excrection profile. Some years ago we reported on the use of Gd-loaded apoferritin [4-6] that displays a relaxivity of ca. 600-800 mM – 1 s –1 per apoferritin. The system is extremely well tolerated, and it is not taken-up by macrophages. The attainable relaxation enhancement of Gd-loaded apoferritin is limited by the number of Gd-HPDO3A (Prohance) units (eight to ten) that is possible to entrap in the inner cavity of the protein with this procedure, based on H + -controlled deassembly/reassembly of