Preoperative 11C-methionine PET imaging in glioma grading efficacy and its predictive value for IDH1 gene mutation status

中华核医学与分子影像杂志 Pub Date : 2020-03-25 DOI:10.3760/CMA.J.CN321828-20190729-00138

Weiyan Zhou, Fengchun Hua, Jianfei Xiao, Ming Li, Yuhua Zhu, Tao Hua

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Abstract

Objective To assess the preoperative 11C-methionine (11C-MET) PET imaging in glioma grading efficacy and its predictive value for isocitrate dehydrogenase enzyme 1 (IDH1) gene mutation status. 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 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 11C-MET imaging. Maximum standardized uptake value (SUVmax), peak standardized uptake value (SUVpeak), tumor-to-background ratio (TBR; SUVmax in lesion/mean standardized uptake value (SUVmean) in normal contralateral cortex) were calculated. Independent-sample t test and one-way analysis of variance were applied to assess the differentiating efficacy of 11C-MET PET imaging for different glioma groups. Based on IDH1 immunohistochemical staining results, predictive efficacy of 11C-MET PET diagnostic parameters on IDH1 mutation status in glioma patients was further analyzed with receiver operating characteristic (ROC) curve analysis. Results Low-grade glioma (LGG; grade Ⅱ) group showed significant differences from high-grade glioma (HGG; grade Ⅲ-Ⅳ) group in SUVmax(2.458±1.100 vs 3.828±1.540; t=5.624, P<0.01), SUVpeak (2.160±0.991 vs 3.261±1.319; t=5.175, P<0.01) and TBR (2.283±0.942 vs 3.434±1.395; t=5.328, P<0.01). SUVmax (2.458±1.100, 3.591±1.611 and 4.251±1.343; F=17.67, P<0.01), SUVpeak(2.160±0.991, 3.040±1.335 and 3.656±1.225; F=15.48, P<0.01) and TBR (2.283±0.942, 3.010±1.242 and 4.192±1.358; F=22.73, P<0.01) were different in grade Ⅱ, Ⅲ and Ⅳ glioma subgroups. SUVmax, SUVpeak 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 P<0.01). SUVmax indicated the best single-parameter prediction performance (area under curve (AUC) =0.808, z=7.193, P<0.01), while the SUVmax + SUVpeak showed the best performance (AUC=0.852, z=9.115, P<0.01). In the subgroup of grade Ⅱ (n=55), TBR of patients with IDH1 gene mutation (n=41) was lower than that of patients with IDH1 wild-types (n=14; 2.152±0.759 vs 2.793±1.208; t=2.326, P=0.02), while TBR of those with oligodendrogenic components (n=26) was higher than that of patients with IDH1 gene mutation only (n=18; 2.383±0.825 vs 1.854±0.478; t=2.447, P=0.02). Conclusions Preoperative semi-quantitative parameters (SUVmax, SUVpeak, TBR) of 11C-MET brain PET imaging have satisfactory grading discrimination performance for glioma patients. SUVmax is the best predictor for IDH1 mutation as a single parameter, while SUVmax + SUVpeak showed the most optimized predictive ability. The oligodendrogenic components in glioma can increase the uptake of 11C-MET, which may affect the effectiveness of 11C-MET in determining glioma grade to some extent. Key words: Glioma; Positron-emission tomography; Methionine; Genes; Mutation; Isocitrate Dehydrogenase

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脑胶质瘤术前11C-甲硫氨酸PET显像分级疗效及其对IDH1基因突变状态的预测价值

目的探讨术前11c -蛋氨酸(11C-MET) PET显像在胶质瘤分级中的疗效及其对异柠檬酸脱氢酶1 (IDH1)基因突变状态的预测价值。方法118例胶质瘤患者(男70例，女48例;中位年龄45岁，年龄范围:10-71岁;回顾性分析2012年2月至2017年11月在华山医院PET中心接受11C-MET PET显像的病例(Ⅱ分级65例，Ⅲ分级34例，Ⅳ分级19例)。对11C-MET成像进行基于病变的半定量分析。最大标准化摄取值(SUVmax)、峰值标准化摄取值(SUVpeak)、肿瘤与背景比(TBR);计算病变SUVmax /正常对侧皮质平均标准化摄取值(SUVmean)。采用独立样本t检验和单因素方差分析评价11C-MET PET成像对不同胶质瘤组的鉴别效果。基于IDH1免疫组化染色结果，进一步采用受试者工作特征(ROC)曲线分析，分析11C-MET PET诊断参数对胶质瘤患者IDH1突变状态的预测效果。结果低级别胶质瘤;级别Ⅱ)组与高级别胶质瘤(HGG;分级Ⅲ-Ⅳ)组SUVmax(2.458±1.100 vs 3.828±1.540;t=5.624, P<0.01)， SUVpeak(2.160±0.991 vs 3.261±1.319;t=5.175, P<0.01)和TBR(2.283±0.942 vs 3.434±1.395;t = 5.328, P < 0.01)。SUVmax分别为2.458±1.100、3.591±1.611和4.251±1.343;F=17.67, P<0.01)， SUVpeak分别为2.160±0.991、3.040±1.335和3.656±1.225;F=15.48, P<0.01)、TBR(2.283±0.942、3.010±1.242、4.192±1.358);F=22.73, P<0.01)，分别为Ⅱ、Ⅲ、Ⅳ级胶质瘤亚组。SUVmax、SUVpeak、TBR在Ⅱ级与Ⅲ级、Ⅱ级与Ⅳ级胶质瘤之间均有统计学差异，Ⅲ级与Ⅳ级胶质瘤与TBR之间也有统计学差异(均P<0.01)。单参数预测效果最好的是SUVmax(曲线下面积(area under curve, AUC) =0.808, z=7.193, P<0.01)，最佳的是SUVmax + SUVpeak (AUC=0.852, z=9.115, P<0.01)。在Ⅱ级亚组(n=55)中，IDH1基因突变患者(n=41)的TBR低于IDH1野生型患者(n=14);2.152±0.759 vs 2.793±1.208;t=2.326, P=0.02)，而具有少突基因成分的患者TBR (n=26)高于仅具有IDH1基因突变的患者(n=18;2.383±0.825 vs 1.854±0.478;t = 2.447, P = 0.02)。结论11C-MET脑PET成像术前半定量参数(SUVmax、SUVpeak、TBR)对胶质瘤患者具有满意的分级鉴别性能。SUVmax作为单参数对IDH1突变的预测效果最好，而SUVmax + SUVpeak的预测能力最优。胶质瘤中少突细胞成分可增加11C-MET的摄取，这可能在一定程度上影响11C-MET判断胶质瘤分级的有效性。关键词:胶质瘤;正电子发射断层扫描;蛋氨酸;基因;突变;异柠檬酸脱氢酶

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来源期刊

中华核医学与分子影像杂志核医学，分子影像

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5088

期刊介绍： Chinese Journal of Nuclear Medicine and Molecular Imaging (CJNMMI) was established in 1981, with the name of Chinese Journal of Nuclear Medicine, and renamed in 2012. As the specialized periodical in the domain of nuclear medicine in China, the aim of Chinese Journal of Nuclear Medicine and Molecular Imaging is to develop nuclear medicine sciences, push forward nuclear medicine education and basic construction, foster qualified personnel training and academic exchanges, and popularize related knowledge and raising public awareness. Topics of interest for Chinese Journal of Nuclear Medicine and Molecular Imaging include: -Research and commentary on nuclear medicine and molecular imaging with significant implications for disease diagnosis and treatment -Investigative studies of heart, brain imaging and tumor positioning -Perspectives and reviews on research topics that discuss the implications of findings from the basic science and clinical practice of nuclear medicine and molecular imaging - Nuclear medicine education and personnel training - Topics of interest for nuclear medicine and molecular imaging include subject coverage diseases such as cardiovascular diseases, cancer, Alzheimer’s disease, and Parkinson’s disease, and also radionuclide therapy, radiomics, molecular probes and related translational research.