TUMOR RESPONSE TO THERAPY CHARACTERIZED BY NMR

表征肿瘤治疗反应的研究

Studies to characterize therapeutic responses of tumors in terms of metabolic, vascular and morphologic changes will be carried out to help identify mechanisms and establish potential predictive indices for tumor control and cure. Nuclear Magnetic Resonance spectroscopy and imaging in viva will be used as noninvasive techniques to monitor the time course of changes in high energy phosphate metabolism, vascularity and necrotic development in tumors subjected to selected therapeutic regimens. An assessment of tumor response in vivo is a desired goal for the evaluation of cancer therapy and NMR provides a noninvasive means to follow in situ the time course of the response within the same tissue. The proposed work will focus on studying the response of subcutaneously implanted rat mammary tumors treated with photodynamic therapy, PDT. Phosphorus NMR spectroscopy will be used to study high energy phosphate metabolism and pH changes; deuterium NMR will be used to follow the uptake of D2O into tumors as a measure of tumor blood flow; proton imaging will be used to monitor and characterize the development of necrosis in the tumor; and fluorine imaging of the distribution of a perfluorocarbon blood substitute will be used to assess the extent of damage to tumor vascularity. Localized spectroscopy and imaging techniques will be applied to determine heterogeneous therapeutic responses in these tumors. Metabolic and vascular changes in regions of tissue, which become necrotic, and regions that undergo reversible metabolic inhibition will be identified and characterized. Tumor growth will be monitored over several weeks following treatment as a measure of long term tumor control. Correlations will be sought between short term metabolic, vascular and morphologic responses following PDT and long term tumor control to aid in the understanding of mechanisms and to ask whether early changes detected by NMR offer the potential of early predictive indices for later tumor response. These results will form the basis of studies to be applied to other selected experimental tumor models and therapies.