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Clinical Research for the Development of The Drug Metabolism Investigation Methods with ^<13>C and ^<19>F-MRS

^<13>C和^<19>F-MRS药物代谢研究方法发展的临床研究

基本信息

批准号：
08457238
负责人：
IKEHIRA Hiroo
金额：
$ 2.62万
依托单位：
CHIBA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457238/
关键词：
^<13>C-MRS ^<19>F-MRS multi nuclei MRS glucose metabolism drug metabolism

项目摘要

Dynamic natura1 abundance ^<13> C-magnetic resonance spectroscopy (^<13>C-MRS) studies without proton decoupling were performed in the human liver using commercial 1.5 T MRI equipment. A single tuned custom-made circular shape surface coil with an outer diameter of 20 cm operating at 16.04 MHz was used for ^<13>C study. Seventy-five grams of glucose dissolved in water was administrered for the natural abundance ^<13>C-MRS dynamic study, which lasted for approximately 40 to 60 minutes. Data acquisition was broken into 20 min and 1.7 min blocks. Localized proton shimming with a whole body coil was performed with adequate volume to include the observing area of the surface coil, and the line width of the water signal was less than 20 Hz. The glucose and glycogen spectra were clearly visible at 80 to 120 ppm after oral administration of glucose solution. These data demonstrate that dynamic hepatic carbohydrate metabolism is possible to observe with commercially available MRI equipment. Giv … More en that the human hepatic glycogen pool reaches the maximum level within less than 10 min, it should allow for the direct diagnosis of hepatic carbohydrate metabolic disorders.Natural abundance ^<19>F-magnetic resonance spectroscopy (^<19>F-MRS) on 5-EU based medicines were performed in the human liver using commercial 1.5 T MRI equipment. A single tuned custom- made circular shape surface coil with an diameter of 15 cm operating at 60 MHz was used for ^<19>F- MRS study. Localized proton shimming with a whole body coil was performed with adequate volume to include the observing area of the surface coil, and the line width of the water signal was less than 20 Hz. Normal clinical dose of oral fluorine anticancer medicine should be too small to detect enough signal for the ^<19>F-MRS using commercial MRI equipment. But we can observe very different spectroscopic appearance patterns of 5-FU.We examined whether the pharmacokinetics in the liver of orally administered 1-hexylcarbamoyl-5-fluorouracil (HCFU) differ from those of orally administered 5'-deoxy-5-fluorouridine (5'-DFUR). This preliminary study indicated ^<19>^<19>F-MRS technique should be very useful method to evaluate in vivo 5-FU based medicines metabolism. Less

使用<13><13>商用1.5 T MRI设备在人体肝脏中进行了动态自然丰度~ 13 C-磁共振波谱（~ 13 C-MRS）研究，未进行质子去耦。使用在16.04 MHz下操作的外径为20 cm的单调谐定制圆形表面线圈进行14 <13>C研究。施用75克溶解在水中的葡萄糖用于天然丰度13 <13>C-MRS动态研究，其持续约40至60分钟。数据采集分为20分钟和1.7分钟的块。使用全身线圈进行局部质子匀场，具有足够的体积以包括表面线圈的观察区域，并且水信号的线宽小于20 Hz。口服葡萄糖溶液后，葡萄糖和糖原光谱在80 - 120 ppm处清晰可见。这些数据表明，动态肝脏碳水化合物代谢是可能的，观察与市售MRI设备。Giv ...更多信息应用1.5T磁共振成像仪对人肝脏进行了天然丰度~ 1F-MRS（Natural丰度~ <19>1F-magnetic resonance <19>spectroscopy）研究。使用一个直径为15 cm的单调谐定制圆形表面线圈，工作频率为60 MHz，用于~ <19>1F-MRS研究。使用全身线圈进行局部质子匀场，具有足够的体积以包括表面线圈的观察区域，并且水信号的线宽小于20 Hz。常规临床口服抗肿瘤药物的剂量太小，以至于<19>用市售MRI设备无法检测到足够的~ 1F-MRS信号。但是我们可以观察到非常不同的5-FU的光谱外观模式。我们研究了口服1-己基氨基甲酰基-5-氟尿嘧啶（HCFU）和口服5 ′-脱氧-5-氟尿嘧啶（5 ′-DFUR）在肝脏中的药代动力学是否不同。初步研究表明，~（<19>13）<19>F-MRS技术是评价5-FU类药物体内代谢的有效方法。少