11C-MET PET显像对术前脑胶质瘤分级判断及对IDH1基因突变的预测价值n

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目的:探讨蛋氨酸(n 11C-MET)PET显像对术前胶质瘤的分级判断及其对异柠檬酸脱氢酶1(IDH1)基因突变的预测价值。n 方法:回顾性分析2012年2月至2017年11月间于华山医院PET中心行n 11C-MET PET显像的118例术前脑胶质瘤患者(男70例,女48例;中位年龄45岁,范围10~71岁;Ⅱ级65例、Ⅲ级34例、Ⅳ级19例),基于病灶对其n 11C-MET摄取值进行半定量分析,计算最大标准摄取值(SUVn max)、标准摄取峰值(SUVn peak)、病灶SUVn max/正常对侧脑皮质平均标准摄取值(TBR)。应用两独立样本n t检验及单因素方差分析评价n 11C-MET脑PET显像对不同级别胶质瘤间的鉴别效能;并结合IDH1免疫组织化学染色结果,应用受试者工作特征(ROC)曲线进一步分析n 11C-MET PET半定量参数对IDH1基因突变状态的预测效能。n 结果:低级别胶质瘤(LGG;Ⅱ级)与高级别胶质瘤(HGG;Ⅲ和Ⅳ级)组SUVn max (2.458±1.100和3.828±1.540;n t=5.624, n P<0.01)、SUVn peak (2.160±0.991和3.261±1.319;n t=5.175, n P<0.01)、TBR(2.283±0.942和3.434±1.395;n t=5.328, n P<0.01)差异均有统计学意义;Ⅱ、Ⅲ和Ⅳ级胶质瘤亚组的SUVn max(2.458±1.100、3.591±1.611和4.251±1.343; n F=17.67, n P<0.01)、SUVn peak(2.160±0.991、3.040±1.335和3.656±1.225; n F=15.48, n P<0.01)和TBR(2.283±0.942、3.010±1.242和4.192±1.358;n F=22.73, n P<0.01)间的差异均有统计学意义,SUVn max、SUVn peak、TBR分别在Ⅱ与Ⅲ级胶质瘤间、Ⅱ和Ⅳ级胶质瘤间,TBR在Ⅲ和Ⅳ级胶质瘤间的差异有统计学意义(均n P<0.01)。单参数分析中,SUVn max预测IDH1突变效能最佳[曲线下面积(AUC)=0.808, n z=7.193, n P<0.01];多参数分析中,SUVn max+SUVn peak预测效能最佳(AUC=0.852, n z=9.115, n P<0.01)。Ⅱ级胶质瘤(n n=55)中,IDH1基因突变者(n n=41)的TBR低于IDH1基因野生型者(n n=14;2.152±0.759与2.793±1.208;n t=2.326, n P=0.02),而含少突成分的胶质瘤患者(n n=26)的TBR高于单纯IDH1突变者(n n=18; 2.383±0.825与1.854±0.478;n t=2.447, n P=0.02)。n 结论:11C-MET脑PET显像半定量参数(SUVn max、SUVn peak、TBR)对术前脑胶质瘤有很好的分级判断效能。SUVn max作为单一参数对IDH1基因突变的预测效能最佳,SUVn max+SUVn peak的多参数预测效能最好。胶质瘤中含少突成分会使n 11C-MET摄取值增高,在一定程度上影响n 11C-MET对胶质瘤级别的判断效能。n “,”Objective:To assess the preoperative n 11C-methionine (n 11C-MET) PET imaging in glioma grading efficacy and its predictive value for isocitrate dehydrogenase enzyme 1 (IDH1) gene mutation status.n Methods:A total of 118 glioma cases (70 males, 48 females; median age 45 years, age range: 10-71 years; Ⅱ grade 65 cases, Ⅲ grade 34 cases, Ⅳ grade 19 cases) received n 11C-MET PET imaging in PET Center of Huashan Hospital from February 2012 to November 2017 were retrospectively analyzed. Lesion-based semi-quantitative analysis was conducted on the n 11C-MET imaging. Maximum standardized uptake value (SUVn max), peak standardized uptake value (SUVn peak), tumor-to-background ratio (TBR; SUVn max in lesion/mean standardized uptake value (SUVn mean) in normal contralateral cortex) were calculated. Independent-sample n t test and one-way analysis of variance were applied to assess the differentiating efficacy of n 11C-MET PET imaging for different glioma groups. Based on IDH1 immunohistochemical staining results, predictive efficacy of n 11C-MET PET diagnostic parameters on IDH1 mutation status in glioma patients was further analyzed with receiver operating characteristic (ROC) curve analysis.n Results:Low-grade glioma (LGG; grade Ⅱ) group showed significant differences from high-grade glioma (HGG; grade Ⅲ-Ⅳ) group in SUVn max(2.458±1.100 n vs 3.828±1.540; n t=5.624, n P<0.01), SUVn peak (2.160±0.991 n vs 3.261±1.319; n t=5.175, n P<0.01) and TBR (2.283±0.942n vs 3.434±1.395; n t=5.328, n P<0.01). SUVn max (2.458±1.100, 3.591±1.611 and 4.251±1.343; n F=17.67, n P<0.01), SUVn peak(2.160±0.991, 3.040±1.335 and 3.656±1.225; n F=15.48, n P<0.01) and TBR (2.283±0.942, 3.010±1.242 and 4.192±1.358;n F=22.73, n P<0.01) were different in grade Ⅱ, Ⅲ and Ⅳ glioma subgroups. SUVn max, SUVn peak and TBR all showed significant differences between grade Ⅱ and grade Ⅲ gliomas, grade Ⅱ and grade Ⅳ gliomas, and there were also statistical differences between grade Ⅲ and grade Ⅳ glioma with TBR (all n P<0.01). SUVn max indicated the best single-parameter prediction performance (area under curve (AUC) =0.808, n z=7.193, n P<0.01), while the SUVn max + SUVn peak showed the best performance (AUC=0.852, n z=9.115, n P<0.01). In the subgroup of grade Ⅱ (n n=55), TBR of patients with IDH1 gene mutation (n n=41) was lower than that of patients with IDH1 wild-types (n n=14; 2.152±0.759 n vs 2.793±1.208; n t=2.326, n P=0.02), while TBR of those with oligodendrogenic components (n n=26) was higher than that of patients with IDH1 gene mutation only (n n=18; 2.383±0.825 n vs 1.854±0.478; n t=2.447, n P=0.02).n Conclusions:Preoperative semi-quantitative parameters (SUVn max, SUVn peak, TBR) of n 11C-MET brain PET imaging have satisfactory grading discrimination performance for glioma patients. SUVn max is the best predictor for IDH1 mutation as a single parameter, while SUVn max + SUVn peak showed the most optimized predictive ability. The oligodendrogenic components in glioma can increase the uptake of n 11C-MET, which may affect the effectiveness of n 11C-MET in determining glioma grade to some extent.n
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