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

动态自然丰度^<13> c -磁共振波谱（^<13>C-MRS）研究没有质子解耦使用商用1.5 T MRI设备在人肝脏进行。在^<13>C的研究中，使用了一个外径为20 cm的定制圆形表面线圈，工作频率为16.04 MHz。75克葡萄糖溶于水，进行自然丰度^<13>的C-MRS动态研究，持续约40 ~ 60分钟。数据采集分为20分钟和1.7分钟两个时间段。用全身线圈进行局部质子闪影，其体积足以包括表面线圈的观测区域，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 ~ 120ppm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。鉴于人肝糖原库在不到10分钟内达到最高水平，应该可以直接诊断肝碳水化合物代谢紊乱。使用商用1.5 T MRI设备在人体肝脏中对5-EU药物进行天然丰度^<19>F-MRS （^<19>F-MRS）。用于^<19>F- MRS研究的是一个直径为15 cm的单调谐定制圆形表面线圈，其工作频率为60 MHz。用全身线圈进行局部质子闪影，其体积足以包括表面线圈的观测区域，水信号的线宽小于20 Hz。口服氟抗癌药物的正常临床剂量应该太小，不足以用商用MRI设备检测到^<19>的F-MRS信号。但是我们可以观察到非常不同的5-FU光谱外观模式。我们检测了口服1-己基氨基甲酰-5-氟尿嘧啶（HCFU）与口服5'-脱氧-5-氟吡啶（5'-DFUR）在肝脏中的药代动力学是否不同。本初步研究表明^<19>^<19>F-MRS技术是评价体内5-FU类药物代谢的一种非常有用的方法。少

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