application) It is proposed to introduce paramagnetic transition metal-substituted heteropoly complexes of tungsten and molybdenum as contrast agents for Magnetic Resonance Imaging. By virtue of changes in proton relaxation rates of water these complexes will enhance image contrast between normal and diseased tissue in the human body. Heteropoly complexes are extremely attractive as a new class of contrast agents owing to their nontoxicity, thermodynamic stability, and their recently reported antiviral and antitumor activity. Tissue specificity is also expected based on their large sizes and/or high molecular weights. Preliminary results on both the relaxivity and the toxicity of the representative gadolinium substituted heteropoly complex confirm the potential of this group of compounds for future clinical applications. Numerous heteropoly complexes will be examined with respect to their relaxivities of water in solution as well as in tissue. The applicants will examine how the following factors affect the relaxivity of heteropoly complexes: (1) presence of inner- vs outer-sphere water of coordination, (2) size and charge of complexes, and (3) delocalization of unpaired electron density over large fragments of a contrast agent. All of the proposed complexes are expected to be excellent contrast agents because of their non-degenerate (S) electronic ground states and large magnetic moments. Owing to the large numbers of existing complexes of various sizes, molecular weights and types of water of coordination (inner- vs outer- sphere), important contributions to the understanding of the relaxivities of contrast agents in general are expected.
