Transition Metal Cluster and Polygadolinium Compounds as a New Paradigm For High Attenuation and/or Relaxivity in Contrast Media Design: Crashing The Molecular r1 = 100 Barrier

Abstract

We have been developing the supporting chemistry for new types of X-ray and MRI contrast agents by exploiting the unique aspects of high atomic number metal cluster compounds and highly paramagnetic, rigid polygadolinium complexes. Octahedral halide clusters of tantalum (Ta) and tungsten (W) should have multiplied attenuation, compared to iodinated contrast media, in X-ray imaging because of their closer absorption match to the emission spectra of radiological equipment. Their substantial absorption at energies >60 kev increases diagnostic S/N and can lower ancillary absorbed dose. Polygadolinium compounds with μ3-hydroxo ligands have substantial magnetic moments, and the lack of Gd antiferromagnetic coupling combined with inner-sphere water coordination and novel outer-sphere H2O H-bonding to the μ3-hydroxos can multiply relaxivity compared to monomeric Gd complexes. Major impediments to the development of these polynuclear compounds as contrast media are low synthetic yields and lack of multidentate ligand coordination chemistry. The objectives of the research are to develop high yield syntheses and the coordination chemistries of known and new polynuclear compounds, to design encapsulating chelates that will impart biocompatibility and facilitate bioconjugation for molecular targeting/imaging, and to measure attenuations and relaxivities.