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Abstract

Bioresponsive or smart contrast agents (SCAs) can substantially improve specificity of magnetic resonance imaging (MRI) in studying processes on molecular and cellular level. These probes are capable of alternating the MR image contrast upon change in the local environment, thus reporting the occurrence of a particular physiological or pathological process. For instance, monitoring of concentration changes of ions or molecules that are involved in neuronal signaling can lead to development of new functional MRI (fMRI) methodology that allows investigation of brain activity in unprecedented fashion. To this end, we prepared and studied a series of paramagnetic and biocompatible SCAs that strongly respond to calcium ions and amino-acid neurotransmitters. Small-sized SCAs exhibited extraordinary properties in vitro, as well as in complex cellular model systems or ex vivo. Yet, we have also developed strategies to modify these SCAs and enable their coupling to diverse nanosized functional molecules. The resulting dendrimeric-, nanoparticle- or liposome-based SCAs strongly affect the MRI signal in presence of the target analyte and exhibit improved biokinetic properties. Furthermore, they possess potential for utilization in novel MRI methodologies that allow rapid monitoring of biological processes. The initial in vivo results with these SCAs are very encouraging, holding great promise for their use in molecular fMRI.