葡萄糖转运蛋白1(GLUT-1)抑制剂BAY-876体内活性的正电子发射型计算机断层显像(PET)检测

Identification of in vivo Activity of Glucose Transpoter(GLUT-1) Inhibitor BAY-876 on Hepatocellular Carcinoma Cells Using Positron Emission Computed Tomography(PET) Analysis

目前,葡萄糖转运蛋白(glucose transporter,GLUT)不仅是细胞摄取葡萄糖的功能与物质保障,同时也是恶性肿瘤抗肿瘤药物治疗的新型干预靶点。建立GLUT抑制剂的体内活性评价方法具有重要意义。利用正电子发射型计算机断层显像检测仪(positron emission computed tomography,PET)对小动物肝细胞癌(hepatocellular carcinoma,HCC)肿瘤模型进行PET检测,建立GLUT抑制剂的小动物体内活性检测方法。在HCC细胞系中检测GLUT-1的表达,选取GLUT-1表达水平最高的细胞系接种BalB/c免疫缺陷动物皮下,形成免疫缺陷动物皮下肿瘤模型。连续三日口服灌胃给药,给予动物5 mg/kg的GLUT-1抑制剂BAY-876后,进行PET检测。动物行尾静脉注射200μCi的核素探针^(18)F-FDG,约30 min后进行PET检测。在此基础上,使用盖革计数器检测动物肿瘤与血液的放射性强度比较。在所选细胞系中,MHCC-97H细胞中GLUT-1的表达显著高于其他细胞系,BAY-876治疗动物能够显著抑制MHCC-97H皮下肿瘤组织对18F-FDG的摄取。GLUT-1抑制剂BAY-876能够显著抑制HCC细胞对葡萄糖的摄取,成功建立了利用PET检测GLUT抑制剂动物体内活性的PET检测方法。

Glucose transporters( GLUTs) mediates the absorbing of glucose in mammal cells. However,the potential application of GLUT inhibitors in hepatocellular carcinoma( HCC) is largely unknown. To identify the in vivo activity of GLUT-1 inhibitor BAY-876 on hepatocellular carcinoma cells using positron emission computed tomography( PET). The expression of GLUT-1 in HCC cell line was identified by qPCR. MGCC-97H cells,which express highest GLUT-1,were injected to nude mice. After 2 ~ 3 weeks growth,mice were treated with control( PBS) or 5 mg/kg BAY-876 once per day for three days. Mice were injected with 200 μCi ^(18)F-FDG and analyzed by PET. MHCC-97H expresses highest GLUT-1 than other cell lines. Treatment of BAY-876 attenuates the absorbing of ^(18)F-FDG in MHCC-97H cells. In inhibitor of GLUT-1,BYA-876,could inhibit the absorbing of glucose in HCC cells. This work established a method to identify the in vivo activity of GLUTs inhibitor.