NMR methods including imaging (MRI) and spectroscopy (MRS) have promise for noninvasive determination of the fraction of cells in tumors which are hypoxic and relatively resistant to radiation therapy and chemotherapy. Similarly, metabolic and other changes in tumors which can be observed and quantified by nondestructive NMR measurements may indicate response to therapy. NMR studies of tumors have shown reproducible differences from normal tissues; differences among tumors of the same line in different stages of growth and differentiation; and differences in tumors following treatment. Yet, with few exceptions, the significance of these results has been vitiated by inadequate localization of NMR signals; use of poorly characterized tumor lines; study of tumor cells maintained in non-physiologic milieus; and lack of important correlative measurements or reference standards. We propose to observe selected MRI and MRS parameters in the BA1112 rhabdomyosarcoma, a stable and well-characterized tumor which can be cultured both in vitro and in vivo. We will study BA1112 cells in a culture system in which perfusion and oxygenation can be controlled and measured. We will model hypoxia and reoxygenation, determine the hypoxic fraction using analyses of survival curves in irradiated culture, and administer """"""""therapeutic"""""""" doses of radiation to BA1112 cells in this mode of culture. We believe that these studies will permit prediction of the hypoxic fraction and analysis of the response to radiation in this model system, and that this information can be transposed to solid BA1112 tumors in WAG/Rij rats. With emphasis on chemical shift imaging, flow and selective volume spectroscopic methods, studies of BA1112 implanted in rats will parallel those performed in the in vitro culture system, modified as required depending upon results obtained in the more easily manipulable in vitro setting. Our ultimate goal is to apply such methods to solid tumors in human patients.
