The overall goal of this proposal is to investigate diverse ferromagnetic, ferrimagnetic, and superparamagnetic materials as potential new contrast agents for NM imaging. Preliminary experiments with coated iron oxide particles suggest that particle magnetization and size, modulated by the spatial distribution in tissue, determine proton relaxation enhancement and resultant MR image contrast. Based upon an improved understanding of relaxation mechanisms, we will develop efficient MR imaging strategies for the diagnosis of primary and metastatic cancer of the liver and spleen. Animal models of focal and diffuse cancer will be developed to allow efficient preclinical screening of novel magnetic particles. Particles with increased relaxivity or improved biodistribution will be matched to pulse sequence techniques optimized for specific diagnostic tasks. Gradient echo and phase contrast sequences, which are remarkably sensitive to the presence of iron oxides in low concentration, will be used to develop MR imaging methods for measurement of particle concentration in tissues. Our preliminary data in rodents and humans suggest that quantitation of reticuloendothelia1 cell function by MRI may allow differential diagnosis of splenic lymphoma and the common benign causes of splenomegaly. LD50, iron metabolism, and other indices of potential toxicity will be used to decide which new materials are suitable for further development as contrast agents.
