Improving the diagnosis of malignancy and pathologic states by medical resonance imaging is a major reason for developing contrast enhancement agents. Sites of malignant melanoma and pancreatic cancer are the targets for the paramagnetic metalloporhyrins proposed herein for investigation; better delineation of lymph nodes to enable evaluation of their own primary pathology and to use their appearance as an index for the presence and extent of malignant disease is also an objective. An in vitro modeling system is proposed to make possible the screening of all compounds in the study for their ability to enhance proton relaxation rates prior to animal evaluation, and the use of the model system is extended to include a fundamental study of those features of the cellular environment responsible for differential contrast between tissues in MRI. Compounds will be tested in plain aqueous media and in aqueous solutions of polymers and polymer gels. Those materials demonstrating most significant enhancement of proton relaxation will be evaluated in Syrian Golden hamsters bearing flank transplanted malignant melanoma or flank transplanted beta-cell adeno-carcinoma of the pancreas; normal Wistar rats are used for nodal studies. Imaging will be scheduled for those compounds which have demonstrated greatest enhancement in vivo. Using the polymer model systems and high resolution NMR, we will examine the validity of the theory that contrast between tissues is determined by the character of the accumulated chance encounters of solute and structure (of water with dissolved macromolecules and surfaces) that occur at the molecular level in the intra- and extracellular regions of samples.
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