The long-term goal of this program project is to develop noninvasive in vivo NMR spectroscopic methods for guiding and monitoring the efficacy of clinical and experimental cancer therapy. These projects represent the application of the most innovative and technically advanced NMR spectroscopy methods to the problem of optimizing therapy choices and protocols and expanding the capabilities of cancer research. 1H, 13C, 19F, and 31P NMR spectroscopic methods will be employed. The program project consists of three closely-related projects in chemotherapy, molecular pharmacology, and radiation therapy. The chemotherapy project (IA) entails study of the predictive correlation between NMR spectra and tumor response to therapy, and of the indicative correlation between changes in NMR spectra after therapy and cytoreduction, vascular function, cytokinetic parameters. Project IB uses NMR for the noninvasive, nonradioactive monitoring of the metabolism of a major chemotherapeutic drug. Project II attempts to exploit the sensitivity of the 31P spectrum to hypoxia, in order to improve the administration of x-irradiation therapy. Each project has, in addition, an important basic tumor biology goal for which NMR offers a unique solution. An NMR core facility will provide state of the art NMR facilities and expertise. Methods will be developed or implemented for the construction of multi-tuned, interleaved probes for monitoring more than one nucleus essentially simultaneously. 1H spectroscopy with carbon decoupling will be implemented for pharmacologic and metabolic studies. NMR microscopy is already being performed on tumors in mice. The development of spatially selective spectroscopy for examination of tumor heterogeneity is a major goal.
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