NMR STUDIES OF HETEROGENEITY & RADIORESISTANCE OF TUMORS

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In vivo magnetic resonance spectroscopy (MRS)/imaging (MRI) has recently been extensively used in investigating the physiology and metabolite alterations of both murine and human neoplasms. It was found that the 31P and 1H MRS are informative in tumor membrane metabolism and bioenergetics, and could potentially be the clinical monitor and/or predictor of tumor response to treatments. However, due to the diversity and complexity of the tumors, the understanding of these alterations from the conventional tumor biochemistry points of view is generally poor and immediate exploration is needed. An extensive correlative study into the physiology and biochemistry of tumor characteristics and their alterations in response to irradiation using both phosphorous and hydrogen MRS in situ and vitro is proposed. In brief: (a) The variation of MRS-observed metabolites and pH of various subpopulations with different ratios of host/tumor cells, Q/P cells, hypoxic fractions, and cell cycle phase distributions will be analyzed and correlated; (b) The effects of subpopulation on intrinsic radioresistance will be examined using MRS in order to elucidate the biological factors which cause the radiation-induced alteration in the metabolites; (c) Ultimately, the significance of in vivo MRS parameters as clinical monitors and/or predictors will be deduced.