An enormous number of biochemical processes taking place in living organisms demands the action of enzymes. These highly specific essential catalysts serve as indicators of diseases (e.g. stroke, brain tumors), cellular processes and are used as essential markers of gene expression. Hence, real-time non-invasive in vivo
mapping of enzyme activity can provide a means for the assessment of disease processes, evaluation of novel therapies (e.g. gene and neuronal stem cell therapies), and also better understanding of biochemical events vital for sustaining life. The aim of this project is to develop a versatile multimodal imaging platform for monitoring the enzyme activity that would allow early disease diagnosis and assessment of cellular events associated with i.e.
gene expression, or monitoring neuronal stem cells after their transplantation.
F MRI and MRS are increasingly gaining an interest and relevance in biomedical and clinical research. The great advantage of 19
F compared to 1
H MRI is the lack of an intrinsic background signal in mammalian tissue, which allows quantitative and unambiguous detection of administered fluorine labeled probes. Accordingly, we have successfully developed a dual-modal 1
F MRI probe, Gd-DOMF-Gal, that can be “lightened on” from an “off” state only in the presence of the enzyme β-galactosidase [see also report of Dr. A. Keliris
. This enzyme is expressed by the LacZ
gene, one of the most widely used reporter genes in transgenic studies. Specific activation of Gd-DOMF-Gal has been proven in vitro
(phantoms, cells) and lately being investigated in in vivo
studies with mice bearing β-galactosidase expressing tumor xenografts (in collaboration with MPI for Metabolism Research, Cologne). Another responsive 1
F MRI probe, which has been recently developed in this line, is sensing the activity of matrix metalloproteinase (MMP-2), an enzyme overexpressed on tumor cells.