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

使用多核磁共振波谱对癌症化疗进行体内监测

基本信息

批准号：
04670720
负责人：
MUNAKATA Tahashi
金额：
$ 1.22万
依托单位：
ASAHIKAWA MEDICAL COLLEGE
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670720/
关键词：
19F NMR SPECTROSCOPY 31P NMR SPECTROSCOPY 5FU(Fluorouracil)Fluoronucleotide Fluoro-beta-alanin

项目摘要

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.

在第一年，我们分析了测量~(19)F核磁共振波谱的基本参数，其中安装了50 mg/ml的5FU。该装置是日本电工株式会社制造的名为GX-270WB的超导核磁共振系统。在共振频率为254.05 MHz、线宽为254.05 MHz、重复频率为100 kHz、重复频率为1 kHz的条件下，得到了具有洛伦兹曲线的~(19)F核磁共振谱。此外，我们还从灌流的大鼠肝脏中获得了光谱。分析了~(19)F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肝脏灌流测定中，可明显观察到5FU及其代谢物FNucts、FuPA和FBAL水平的变化。第二年，在第一年结果的基础上，我们尝试制作了一个核磁共振探针和一个用于活体测量的线圈。第一步是检查来自皮肤和肌肉的信号在表面线圈和肝脏之间的影响。利用装有磷酸溶液的直径为1.0 mm的微型样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%或以上的区域与线圈的距离为4.0-6.0 mm。这个区域与肝脏的解剖区域很好地对应。由于线圈边缘的线圈附近也存在信号，因此来自肌肉和皮肤的信号也被包括在光谱中。表面线圈法无需手术即可检测大鼠肝脏的代谢变化。在此条件下，静脉注射5FU可清楚地观察到麻醉大鼠肝内代谢的变化。结论：结合~(31)P和~(19)F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。