A major theme of the program is to develop the foundations for rational application to clinical oncology of the metabolic and physiochemical information obtainable by NMR. To that end, this project will use in vivo 3IP- and IH-NMR spectroscopy to characterize and study the metabolism of a series of three animal tumors of varying malignancy (Morris hepatomas 7787, 5123 and 77777), as well as two control tissues (normal and post- partial hepatectomized liver). A unique feature of the study is the use of isolated, arterially perfused solid tumor preparations, analogous to perfused organs. This will permit a variety of NMR experiments not easily performed on either cultured tumor cells or animal tumors in situ. Specific issues addressed include: 1. Are there NMR detectable markers, or dynamic features of tumor metabolism, which correlate with degree of malignancy? 2. To what extent are the relatively prolonged proton NMR relaxation times observed in tumors due to intrinsic properties of the tumor cells vs. physiological features of the tumor tissue such as extracellular space, perfusion rate, pH, etc.? 3. Are pH regulation, and the interaction between tissue pH and metabolism different in normal vs. malignant tissue? 4. Can NMR probes (e.g., halothane) reveal significant differences in tumor lipid or membrane composition? Thus, this study will address fundamental in the biology of solid tumors, as well as provide an experimental framework for the eventual application of in vivo NMR measurements to clinical diagnosis and therapeutic monitoring of cancer.
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