Paramagnetic Lanthanoid Compexes


Magnetic Resonance Imaging (MRI) is one of the most important diagnostic tools in modern medicine. MRI is based on the measurement of Nuclear Magnetic Resonance (NMR) of certain atomic nuclei in the body. Of the most abundant chemical elements, hydrogen (or more specifically the isotope 1H) is the most suitable. This is due to its superior magnetic properties and also due to the fact that hydrogen is a major component of almost every important constituent of biological matter (e.g. water, proteins, lipids, etc.).



While MRI can be measured solely on biological material, the use of internalized MRI contrast agents often improves the detection of abnormal tissues (e.g. in tumors).



Almost all modern contrast agents are used for the enhancement of 1H NMR. One promising alternative is the use of 19F atoms instead of hydrogen nuclei. Fluorine naturally consists to 100% of the NMR-active isotope 19F, has a nuclear spin of 1/2, and has a high intrinsic sensitivity which almost matches the one for 1H. In addition, the resonance frequency is very similar to the one for 1H which potentially allows for  the use of the existing 1H MRI scanner infrastructure for 19F measurements.



Since fluorine is essentially absent in the human body, 19F MRI measurements do not suffer any interference from a background signal. On the other hand, this requires the introduction of artificial, fluorinated probes. Unfortunately, the concentrations necessary for practical measurements are quite high (ca. 50 mM) which strongly limits the applicability.

One of the ways to overcome this problem was recently introduced by David Parker et. al. (see. Chem. Eur. J. 2010, 16, 134-148). The principle is to enhance the signal intensity by bringing the fluorine nucleus into the vicinity of a paramagnetic center which speeds up the magnetic relaxation considerably and thus allows a higher frequency of measurements. This in turn increases the signal in a given time interval. The use of this paramagnetic enhancement promises to lower the necessary probe concentrations into the sub-mM range which would represent a major step towards the clinical application of 19F MRI.



Among the best candidates for the above mentioned paramagnetic centers are the lanthanoids (Ln) because of their very unique magnetic and chemical properties (e.g. short relaxation times for almost all paramagnetic Ln). In this context, we are developing highly fluorinated lanthanoid cryptates which have the schematic structure as follows:



Our goal is the in-vivo imaging of various  biomedically relevant phenomena (e.g. cardiovascular inflammation processes).