AN IN VIVO MONITOR OF CHEMOTHERAPY FOR CANCER USING MULTI-NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

在第一年，我们分析了用于从其中安装有50 mg/ml的5 FU的体模测量19 F NMR光谱的基本参数。实验装置为日本电气株式会社生产的GX-270 WB FT-NMR超导核磁共振仪，在共振频率254.05MHz，线宽100 kHz，重复时间100 kHz，共振频率100 MHz，共振频率100 kHz，共振频率100 MHz，共振频率1000 MHz，共振频率100 kHz，共振频率1000 MHz，共振频率100 kHz，共振频率1此外，我们获得了灌注大鼠肝脏的光谱。分析19 F信号强度与肝内氟浓度的关系。大约100 nmol的氟足以在10分钟内进行测量。在用5 FU灌注的肝脏的测量中，清楚地观察到5 FU及其代谢物即FNucts、FUPA和FBAL的水平的变化。第二年，在第一年研究结果的基础上，我们尝试制作了一个核磁共振探针和一个线圈，用于体内测量。第一步是检查来自表面线圈和肝脏之间的皮肤和肌肉的信号的影响。用装有磷酸溶液的1.0mm微样品管测量了表面线圈下的信号强度分布。信号强度为最大信号50%或以上的区域距离线圈4.0 - 6.0 mm。该区域很好地对应于肝脏的解剖区域。由于在线圈的边缘处也存在线圈附近，因此来自肌肉和皮肤的信号被包括在光谱中。表面线圈法可在不经手术的情况下检测大鼠肝脏的代谢变化。在此条件下，从麻醉大鼠中清楚地观察到静脉注射5 FU的肝内代谢变化。结论：31 P和19 F核磁共振波谱结合可以同时监测抗癌药物代谢和癌组织能量代谢的变化。

In the first year, we analyzed the basic parameters for the measurement of 19F NMR spectroscopy from the phantom in which 50mg/ml of 5FU was mounted. The apparatus was a superconducting NMR system named GX-270WB FT-NMR built by NIHON DENNSI Co.Ltd. 19F NMR spectra with Lorentzian curve were obtained under following parameters, resonant frequency ; 254.05MHz, line width ; 100kHz, Repetition time ; 1, . Furthermore we obtained spectra from perfused rat livers. The relationship between the strength of 19F signal and the intrahepatic concentration of fluorine was analyzed. Approximately 100nmol of fluorine was enough for the measurement within ten minutes. In the measurement of liver perfused with 5FU, changes in the level of 5FU and its metabolites i.e. FNucts, FUPA and FBAL were clearly observed. In the second year, with the basis of the results in 1st year, we tried to create a NMR probe and a coil for in vivo measurement. The first step was to examine the effects of the signal from skin and muscle between the surface coil and the liver. The distribution of signal intensity under the surface coil was measured using 1.Omm diameter micro sample tube in which the phosphoric acid solution was mounted. The region having a signal intensity 50% or more of maximal signal was 4.0 - 6.0 mm distance from the coil. This region well corresponds to the anatomical region of the liver. Since also exists near the coil at the edge of the coil, signals from muscle and skin were included the spectra. Surface coil method could detect the metabolic changes from the rat liver without surgical procedure. Under this condition, intrahepatic metabolic changes of the 5FU injected intravenously were clearly observed from anesthetized rat. It is concluded that combination of 31P and 19F NMR spectroscopy can simultaneously monitor the metabolism of anti-cancer drug and the changes in energy metabolism of cancer tissue.