<^(19)F> NMR Study of Fluorinated Compounds in vivo with a view to Medical Application.

1.本项目的目的是利用F-19核磁共振对包括含氟药物在内的含氟化合物进行体内生物化学基础研究，以期应用于医学领域。我们成功地构建了由吸入麻醉剂、氟烷和甲氧基氟烷组成的体模，作为大脑的模型吸附在脂类分散体上，构建了F-19核磁共振化学位移图像。我们开发了新的、改进的氟化合物的合成方法，包括用于监测葡萄糖利用的药物2-脱氧-2-氟-D-葡萄糖(FDG)、2-脱氧-2-氟-D-甘露糖(FDM)和2-脱氧-2-氟-D-半乳糖。用~(19)F-核磁共振研究了FDG在小鼠体内的代谢去向。研究发现，注射到小鼠体内的FDG可转化为FDM(或FDM-6-磷酸)。FDG注射证明该反应是可逆的，即FDG以FDG-6-磷酸和FDG-6-磷酸的形式在组织中积聚。本研究修正了以往关于FDG在高糖代谢部位的捕获机制的概念。FDG和FDGal的F-19核磁共振图像是在2~3 mM或以下的氟化己糖浓度下从小鼠脑片和全身拍摄的。虽然这些图像的对比度和分辨率在现阶段并不令人满意，但目前的结果为该方法的未来发展提供了强有力的前景。我们希望通过在强磁场下使用F-19成像系统来继续这一项目。

1. The purpose of this project is a basic in vivo biochemical study of fluorine compounds including fluorine containing pharmaceuticals with a view to medical application by the use of F-19 NMR.2. We succeeded in the construction of a F-19 NMR chemical shift image with a phantom consists of inhalation aneshetics, halothane and methoxyflurane, adsorbed to the lipid dispersions as a model of brain.3. We developed new, improved synthetic methods of fluorine compounds including 2-deoxy-2-fluoro-D-glucose(FDG) a pharmaceutical used for the monitoring of glucose utilization, 2-deoxy-2-fluoro-D-mannose(FDM), and 2-deoxy-2-fluoro-D-galactose.4. The metabolic fate of FDG was studied in mice with excised organs by F-19 NMR. It was found that FDG injected to mice was converted to FDM(or FDM-6-phosphate) in vivo. The reaction was proved to be reversible by FDM injection, i.e., FDG is accumulated in tissues in the form of FDG-6-phos-phate and FDM-6-phosphate. The previous concept of FDG trapping mechanism at the site of high glucose metabolism was revised by this study.5. The F-19 NMR images of FDG and FDGal were made from a slice of brain and a whole body of mice with the concentrations of fluorinated hexose of 2 - 3 mM or less. Although the contrast and the resolution of these images were not satisfactory at the present stage, the present result gives a strong promise to the future development of this method.6. We hope to continue this project by the employment of F-19 imaging system at high magnetic field.