The proposed investigation represents an application of nuclear magnetic resonance (NMR) to the study of neoplastic diseases. These experiments will focus on F19 NMR to detect tumors and monitor their response to therapeutic maneuvers. F19 NMR has been shown to be valuable in the study of cells, membranes and fluorinated anesthetics. We intend to use a non-toxic, parentally administered perfluorochemical emulsion - Fluosol-DA - for this study. Fluosol-DA is concentrated in reticulo-endothelial organs and has been shown to accumulate in tumors. It has also been shown to be a radiosensitizing agent when used in conjunction with carbogen. We intend to take advantage of these characteristics by investigating the feasibility of detecting Fluosol-DA in tumors with F19 NMR surface coil spectroscopy and imaging, and maximizing the radiosensitization effect by optimizing tumor Fluosol-DA content. Initial studies will be aimed at defining the in-vitro and in-vitro NMR characteristics of Fluosol-DA (spectra, T1 and T2) and optimization of imaging equipment for F19 NMR. Surface coil spectroscopy will be used to study the uptake and clearance rate of Fluosol-DA in normal tissues, abscesses and tumors. Imaging studies to determine if F19 NMR can detect Fluosol-DA in tumors will also be done. The radiosensitization effect of Fluosol-DA and oxygen will be maximized by varying the quantity and schedule of Fluosol-DA administration. The effectiveness of Fluosol-DA as a radiosensitizer will be monitored by comparing Fluosol-DA content of the tumor (measured in-vivo by F19 NMR) with tumor growth delay. Tumor metabolism of 5-Fluorouracil (5FU) will be studied to determine if in-vivo metabolic profiles can predict tumor sensitivity or resistance. Preliminary data suggest that concentrations of 5-fluorodeoxyuridylate, a metabolite of 5FU, are useful in predicting tumor sensitivity.
