人脑胶质瘤PET成像中^(11)C-蛋氨酸摄取与LAT1和4F2hc表达的关系

Relation of ^(11)C-MET Uptake in PET with LAT1 and 4F2hc Expression in Human Brain Gliomas

背景与目的:以11C-蛋氨酸(11C-MET)为示踪剂的正电子发射体层成像(PET)可为脑肿瘤的氨基酸代谢提供重要信息,大型氨基酸转运载体1(LAT1)和细胞表面抗原4F2重链(4F2hc)所形成的LAT1/4F2hc复合物是包括蛋氨酸在内的大型、中性氨基酸的主要转运载体,本研究旨在探讨人脑胶质瘤中11C-MET摄取量与LAT1和4F2hc表达的关系。方法:对30例新诊断的脑胶质瘤患者行11C-MET PET检查,计算11C-MET最大标准化摄取值(SUVmax);采用免疫组化方法检测LAT1和4F2hc在相同脑胶质瘤标本中的表达;分析11C-METSUVmax、LAT1和4F2hc表达水平与胶质瘤临床病理学特征的关系以及三者之间的关系。结果:11C-METSUVmax、LAT1和4F2hc表达均随胶质瘤病理级别的升高而明显增强(P=0.000,P=0.028,P=0.003),在高恶性度胶质瘤中11C-MET SUVmax、LAT1和4F2hc表达也均明显强于低恶性度胶质瘤(P=0.000,P=0.032,P=0.004);LAT1和4F2hc表达之间存在明显正相关(P=0.036);11C-MET SUVmax与LAT1表达也存在明显正相关(P=0.003),但与4F2hc表达无明显相关性(P=0.366)。结论:11C-MET摄取量以及LAT1和4F2hc表达与脑胶质瘤的病理学特征关系密切,LAT1高表达可能是脑胶质瘤11C-MET摄取量增高的一个重要因素。

BACKGROUND ＆ OBJECTIVE： Positron emission tomography （PET） with 11C-methionine （11C-MET） as the tracer can provide important information on the amino acid metabolism of brain tumors. The LAT1/ 4F2hc complex formed by large-type amino acid transporter 1 （LAT1） and cell surface antigen 4F2 heavy chain（4F2hc） is a major transportation system for the large neutral amino acids including methionine. The aim of our study was to investigate the relation of ＇1C-MET uptake with LAT1 and 4F2hc expression in human brain gliomas. METHODS： PET examination with HC- MET was performed in 30 cases of newly diagnosed glioma patients, and the maximal standardized uptake value （SUVmax） of uC-MET was measured. Expressionof LAT1 and 4F2hc was examined by immunohistochemistry in the glioma tissues of the 30 patients. The relation of IIC-MET SUVmax as well as LAT1 and 4F2hc expression level with the clinical and pathological features of gliomas, and their relation with each other, were analyzed. RESULTS： All the IIC-MET SUVmax as well as LAT1 and 4F2hc expression level increased significantly with the asending pathological grade of glioma （/9 = 0.000, P = 0.028, P = 0.003）, and was found significantly higher in malignant glioma tissues than those in benign glioma tissues （P = 0.000, P = 0.032, P = 0.004）. There was a significant positive correlation between LAT1 expression level and 4F2hc expression level （P = 0.036）. HC-MET SUVmax was significantly positively correlated with LAT1 expression level （P = 0.003）, but not with 4F2hc expression level （P = 0.366）. CONCLUSION： 11C-MET SUVmax as well as LAT1 and 4F2he expression are closely associated with the pathological features of brain gliomas. LAT1 overexpression may be an important factor for the increase of 11C-MET in brain gliomas.