Datensatz

Zusammenfassung

Magnetic resonance imaging (MRI) has evolved into a powerful tool in modern biomedical research. Its signal specificity can be further improved using contrast agents and their application has largely contributed to the MRI development. The aim of our group is to develop new measurement techniques that would enable visualization of neuronal activity and better understanding of brain function by using responsive (or 'smart') agents. These are biochemical markers that alter their MR signal upon a certain biochemical event due to changes in their microenvironment. Calcium is an excellent marker tightly linked to brain activation, which has typically been the preferred target for a number of optical imaging methods. To accomplish our goals, we synthesize and study smart MRI contrast agents, complexes that respond to differing concentrations of endogenous Ca2+ by altering their magnetic properties. Over the past years we have reported a number of Gd3+ chelates linked to modified Ca2+ chelators that act as smart MRI contrast agents.[1] Some of the agents exhibited remarkable sensitivity towards Ca2+, and their physicochemical characteristics were found to be superior to any other previously described Ca2+-sensitive MRI agents.[2] In parallel, we developed a series of fluorine-containing complexes with a range of paramagnetic and diamagnetic ions. They exhibit high proton longitudinal relaxivities while displaying an increase in 19F relaxation rates which are favorable for 19F MRI experiments.[3] Subsequently, the complexes that contain a Ca2+ chelator in between the paramagnetic and fluorine-containing moieties are prepared and they are capable of reporting the changes in Ca2+ concentrations simultaneously by 1H and 19F MRI. Extensive studies revealed mechanisms which underly the intramolecular changes triggered by Ca2+, and are responsible for the alternation of the MRI signals at both frequencies.[4] A new generation of dual-frequency probes suitable for both 1H and 19F MRI opens novel perspectives for successful assessment of Ca2+ in living organisms. The ability to observe its concentration changes in a non-invasive fashion would be of paramount importance for MRI methodology advancements and biomedical research in general. The presentation will give a brief overview of smart MRI contrast agents recently studied and reported by our group.