MOLECULAR ASPECTS OF MRI CONTRAST AGENTS SELECTIVITY

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Contrast-enhanced magnetic resonance imaging (MRI) is a very effective clinical diagnostic technique. However, most paramagnetic contrast agents (PCA) enhance image contrast purely on the basis of nonspecific bio- distribution properties, which is sometimes enough to visualize some biochemical events. Currently, there are some gaps in understanding of the structure-function relationship of PCA, molecular mechanism of reversible binding of PCA to biological micromolecules, and the effect of biological environment on relaxivity of PCA. The broad objectives of the proposed project are to understand molecular aspects of binding and interactions of PCA molecules developed for clinical MRI applications with several key biomolecules, such as plasma proteins and phospholipids, and the relationship between binding and relaxation enhancement. The goal will be achieved by characterization of binding interaction and by investigating effects of these interactions on structure and electronic properties of PCA's through systematic study of several classes Gd3+ complexes by a variety of spectroscopic techniques, including fluorescence, nuclear magnetic resonance, and electron paramagnetic resonance at multiple and high frequencies. This key information is essential to guide development of new, more effective contrast agents with enhanced relaxivity and selectivity.