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

第一年，我们分析了安装50mg/ml 5FU的幻影19F NMR波谱测量的基本参数。该装置为日本电芯公司研制的超导核磁共振系统GX-270WB FT-NMR。在以下参数下得到具有洛伦兹曲线的19F核磁共振波谱：谐振频率；254.05MHz，线宽；100kHz，重复时间；1,。此外，我们还获得了灌注大鼠肝脏的光谱。分析19F信号强度与肝内氟浓度的关系。大约100nmol的氟足以在10分钟内进行测量。在5FU灌注肝脏的测量中，可以清楚地观察到5FU及其代谢物FNucts、FUPA和FBAL水平的变化。第二年，在第一年成果的基础上，我们尝试创建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1测量表面线圈下的信号强度分布。1毫米直径的微型样品管，其中安装磷酸溶液。信号强度为最大信号50%或以上的区域距离线圈为4.0 - 6.0 mm。这个区域与肝脏的解剖区域非常吻合。由于在线圈边缘的线圈附近也存在信号，来自肌肉和皮肤的信号被包括在光谱中。表面线圈法无需手术即可检测大鼠肝脏代谢变化。在此条件下，可以清楚地观察到麻醉大鼠静脉注射5FU的肝内代谢变化。综上所述，结合31P和19F核磁共振波谱可以同时监测抗癌药物的代谢和肿瘤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.