Synthesis of High Affinity Contrast Agents for Targeted MR Neuroimaging

Magnetic resonance imaging (MRI) has become one of the essential noninvasive diagnostic techniques for soft tissues and diseases. Contrast agents have been developed to produce additional contrast and increase the signal intensity for MRI [1]. Here we report on the synthesis development of target specific contrast agents for MR neuroimaging. Monomeric and dendrimeric targeted contrast agents (TCA) were synthesized taking advantage of the highly specific interaction of the protein avidin with its ligand biotin [2]. The classical monomeric CAs have disadvantages such as non-specificity, fast renal excretion, low contrast efficiency and therefore they require a high dosage. To overcome this problem, we use multivalent, highly-branched dendrimeric molecules that are capable of carrying large number of CAs and hence the MRI amplification [3]. The TCAs are additionally labeled with a fluorescent dye, for to achieve their multimodal detection by means of optical and MR-based techniques. Upon their preparation, the biotinylated TCAs are suitable for labeling genetically engineered cell surface receptors that contain avidin. [4]. The preliminary experiments showed that TCAs bind specifically to avidin-coated beads (Figure 1). Their further characterization ensures exciting progress in neuroimaging enabling high resolution MRI of specific neuronal populations