11C-MET PET/CT筛查幕上较低级别胶质瘤IDH和1p/19q分子分型的应用价值

doi:10.3969/j.issn.1006-7795.2022.06.002

摘要/Abstract

摘要： 目的评估¹¹C-蛋氨酸(¹¹C-methionine,¹¹C-MET)正电子发射型计算机断层显像／电子计算机断层显像(positron emission tomography/computed tomography, PET/CT) 半定量参数在筛查幕上较低级别胶质瘤(lower-grade glioma, LrGG)异柠檬酸脱氢酶(isocitric dehydrogenase, IDH)突变以及1p/19q共缺失状态的应用价值。方法分析37例幕上较低级别胶质瘤患者术前¹¹C-MET PET/CT图像以及病理学资料。测量¹¹C-MET PET/CT图像上病灶最大肿瘤／正常组织摄取比值(maximum tumor/normal tissue uptake ratio, TNR_max)、平均肿瘤／正常组织摄取比值(mean TNR, TNR_mean)以及肿瘤／正常组织摄取比值峰值(peak TNR, TNR_peak)。根据IDH基因突变以及1p/19q共缺失状态,将患者分为3组:IDH野生型(IDH^wt),IDH突变-1p/19q共缺失型(IDH^mut1p/19q^del)以及IDH突变-1p/19q非共缺失型(IDH^mut1p/19q^int)。比较不同分子分型的LrGG间的TNR_max、TNR_mean以及TNR_peak。使用受试者工作特征(receiver operating characteristic,ROC)曲线分析单参数对于IDH突变和1p/19q共缺失状态的筛查效能。采用Logistic回归建立联合诊断模型,对预测概率进行ROC分析,评估多参数联合筛查效能。结果 TNR_max、TNR_mean、TNR_peak在3组LrGG间的差异有统计学意义(P<0.05)。IDH^wt组TNR_max、TNR_mean、TNR_peak最高,其次为IDH^mut1p/19q^del组,IDH^mut1p/19q^int组最低。IDH^wt LrGG的TNR_max、TNR_mean、TNR_peak均高于IDH^mut LrGG组,差异有统计学意义(P<0.05)。ROC曲线分析结果显示, TNR_max、TNR_mean、TNR_peak筛查LrGG IDH突变的曲线下面积( area under the curve, AUC)分别为0.827、0.847、0.807,以3.09、1.84和2.58为阈值,准确率分别为70.3%、75.7%和75.7%,采用Logistic回归分析构建的筛查模型能提高诊断准确率, AUC值为0.943,灵敏度、特异度和准确率分别为100%、83.3%和94.6%。TNR_max、TNR_mean、TNR_peak筛查LrGG 1p/19q共缺失的AUC分别为0.766、0.792、0.812,以3.35、1.44和2.02为阈值,准确率分别为76.0%、80.0%和80.0%。Logistic筛查模型不能提高诊断效能。结论 ¹¹C-MET PET/CT有助于筛查幕上较低级别胶质瘤IDH突变以及1p/19q共缺失状态。多参数联合能够提高对于IDH基因突变的筛查效能。

关键词: 较低级别胶质瘤, ¹¹C-蛋氨酸, 正电子发射型计算机断层显像, 异柠檬酸脱氢酶, 1p/19q

Abstract: Objective To evaluate the value of ¹¹C-methionine (¹¹C-MET ) positron emission tomography/computed tomography (PET/CT) in screeningisocitric dehydrogenase (IDH) mutation and 1p/19q co-deletion status in supratentorial lower-grade glioma (LrGG). Methods The preoperative ¹¹C-MET PET/CT images and pathological data of 37 patients with lower-grade supratentorial glioma were retrospectively analyzed. The maximum tumor/normal tissue ratio (TNR_max), mean tumor/normal tissue ratio (TNR_mean) and peak tumor/normal tissue ratio (TNR_peak) of lesions on were measured. According to IDH gene mutation and 1p/19q co-deletion status, patients were divided into three groups: IDH wild type (IDH^wt); IDH mutation-1p/19q co-deletion type (IDH^mut1p/19q^del) and IDH mutation-1p/19q intact type (IDH^mut1p/19q^int). TNR values of different molecular subtypes of LrGG were compared with each other. The differential diagnostic efficacy of semi-quantitative parameters for different molecular subtypes of LrGG was analyzed using receiver operating characteristic (ROC)curve. Logistic regression was used to establish a joint diagnostic model, and the ROC analysis was conducted to evaluate the predictive efficiency of joint diagnostic model. Results There were significant differences in TNR_max, TNR_mean and TNR_peak among the three groups of LrGG (P<0.05). TNR_max, TNR_mean and TNR_peak were the highest in the IDH^wt group, followed by the IDH^mut1p/19q^del group. Semiquantitative values were the lowest in the IDH^mut1p/19q^int group. The TNR_max, TNR_mean and TNR_peak of IDH^wt LrGG were higher than those of IDH^mut LrGG, and the difference was statistically significant(P<0.05). The results of ROC analysis showed that the area under the curves (AUCs) of TNR_max, TNR_mean, and TNR_peak for screening IDH mutations were 0.827, 0.847, and 0.807, with thresholds of 3.09, 1.84, and 2.58, respectively, and the accuracy rates were 70.3%、75.7% and 75.7%, respectively. The screening model based on Logistic regression analysis can improve diagnostic accuracy, with an AUC value of 0.943, sensitivity, specificity, and accuracy of 100%, 83.3%, and 94.6%, respectively. The TNR_max, TNR_mean and TNR_peak of IDH^mut1p/19q^del LrGG were significantly higher than those of IDH^mut1p/19q^int LrGG (P<0.05). The AUCs of TNR_max, TNR_mean, and TNR_peak for predicting 1p/19q co-deletion of IDH^mut LrGG were 0.766, 0.792, and 0.812, with thresholds of 3.35, 1.44, and 2.02, respectively, and the accuracies were 76.0%, 80.0%, and 80.0%, respectively. Joint diagnostic model cannot improve diagnostic efficiency. Conclusion ¹¹C-MET PET/CT is helpful for screening IDH mutation and 1p/19q co-deletion status in supratentorial lower-grade gliomas. The combination of multiple parameters can improve the efficiency of screening IDH gene mutation.

Key words: lower-grade glioma, ¹¹C-methionine, positron-emission tomography, isocitric dehydrogenase, 1p/19q

中图分类号:

张姝, 王凯, 杨子皓, 乔真, 李晓桐, 袁磊磊, 艾林. ¹¹C-MET PET/CT筛查幕上较低级别胶质瘤IDH和1p/19q分子分型的应用价值[J]. 首都医科大学学报, 2022, 43(6): 826-833.

Zhang Shu, Wang Kai, Yang Zihao, Qiao Zhen, Li Xiaotong, Yuan Leilei, Ai Lin. Application of ¹¹C-MET PET/CT in screening isocitric dehydrogenase and 1p/19q status in supratentorial lower-grade gliomas[J]. Journal of Capital Medical University, 2022, 43(6): 826-833.

参考文献

[1] The Cancer Genome Atlas Research Network. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas [J]. N Engl J Med, 2015, 372(26): 2481－2498.
[2] Yang X F, Lin Y, Xing Z, et al. Predicting 1p/19q codeletion status using diffusion-, susceptibility-, perfusion-weighted, and conventional MRI in IDH-mutant lower-grade gliomas [J]. Acta radiol, 2021, 62(12): 1657－1665.
[3] Liu Z Y, Zhang T, Jiang H, et al. Conventional MR-based preoperative nomograms for prediction of IDH/1p19q subtype in low-grade glioma [J]. Acad Radiol, 2019, 26(8): 1062－1070.
[4] Park S I, Suh C H, Guenette J P, et al. The T2-FLAIR mismatch sign as a predictor of IDH-mutant, 1p/19q-noncodeleted lower-grade gliomas: a systematic review and diagnostic meta-analysis [J]. Eur Radiol, 2021, 31(7): 5289－5299.
[5] 王康, 靳峰. 弥漫性低级别胶质瘤的临床影像学及分子病理分型的相关研究进展 [J]. 中华神经医学杂志, 2020, 19(6): 562－565.
[6] Gupta M, Gupta T, Purandare N, et al. Utility of flouro-deoxy-glucose positron emission tomography/computed tomography in the diagnostic and staging evaluation of patients with primary CNS lymphoma [J]. CNS Oncol, 2019, 8(4): CNS46.
[7] Song S S, Wang L M, Yang H W, et al. Static ¹⁸F-FET PET and DSC-PWI based on hybrid PET/MR for the prediction of gliomas defined by IDH and 1p/19q status [J]. Eur Radiol, 2021, 31(6): 4087－4096.
[8] Katsanos A H, Alexiou G A, Fotopoulos A D, et al. Performance of ¹⁸F-FDG, ¹¹C-methionine, and ¹⁸F-FET PET for glioma grading: a meta-analysis [J]. Clin Nucl Med, 2019, 44(11): 864－869.
[9] Kim D, Chun J H, Kim S H, et al. Re-evaluation of the diagnostic performance of ¹¹C-methionine PET/CT according to the 2016 WHO classification of cerebral gliomas [J]. Eur J Nucl Med Mol Imaging, 2019, 46(8): 1678－1684.
[10] 周维燕, 华逢春, 肖见飞, 等. 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 [J]. 中华核医学与分子影像杂志, 2020, 40(3): 153－158.
[11] Riva M, Lopci E, Castellano A, et al. Lower grade gliomas: relationships between metabolic and structural imaging with grading and molecular factors [J]. World Neurosurg, 2019, 126: e270-e280.
[12] Gupta N, Singh N. To evaluate prognostic significance of metabolic-derived tumour volume at staging 18-flurodeoxyglucose PET-CT scan and to compare it with standardized uptake value-based response evaluation on interim 18-flurodeoxyglucose PET-CT scan in patients of non-Hodgkin's lymphoma (diffuse large B-cell lymphoma) [J]. Nucl Med Commun, 2020, 41(4): 395－404.
[13] Law I, Albert N L, Arbizu J, et al. Joint EANM/EANO/RANO practice guidelines/SNMMI procedure standards for imaging of gliomas using PET with radiolabelled amino acids and [¹⁸F]FDG: version 1.0 [J]. Eur J Nucl Med Mol Imaging, 2019, 46(3): 540－557.
[14] Ichimura K, Pearson D M, Kocialkowski S, et al. IDH1 mutations are present in the majority of common adult gliomas but rare in primary glioblastomas [J]. Neuro Oncol, 2009, 11(4): 341－347.
[15] Okita Y, Shofuda T, Kanematsu D, et al. The association between ¹¹C-methionine uptake, IDH gene mutation, and MGMT promoter methylation in patients with grade Ⅱ and Ⅲ gliomas [J]. Clin Radiol, 2020, 75(8): 622－628.
[16] Kong Z R, Zhang Y C, Liu D L, et al. Role of traditional CHO PET parameters in distinguishing IDH, TERT and MGMT alterations in primary diffuse gliomas [J]. Ann Nucl Med, 2021, 35(4): 493－503.
[17] Ogawa T, Kawai N, Miyake K, et al. Diagnostic value of PET/CT with ¹¹C-methionine (MET) and ¹⁸F-fluorothymidine (FLT) in newly diagnosed glioma based on the 2016 WHO classification [J]. EJNMMI Res, 2020, 10(1): 44.
[18] Liu F M, Gao Y F, Kong Y Y, et al. The diagnostic value of lower glucose consumption for IDH1 mutated gliomas on FDG-PET [J]. BMC Cancer, 2021, 21(1): 83.
[19] Hartmann C, Hentschel B, Wick W, et al. Patients with IDH1 wild type anaplastic astrocytomas exhibit worse prognosis than IDH1-mutated glioblastomas, and IDH1 mutation status accounts for the unfavorable prognostic effect of higher age: implications for classification of gliomas [J]. Acta Neuropathol, 2010, 120(6): 707－718.
[20] Xing Z, Yang X, She D, et al. Noninvasive assessment of IDH mutational status in World Health Organization grade Ⅱ and Ⅲ astrocytomas using DWI and DSC-PWI combined with conventional MR imaging [J]. AJNR Am J Neuroradiol, 2017, 38(6): 1138－1144.
[21] Zhao J, Wang Y L, Li X B, et al. Comparative analysis of the diffusion kurtosis imaging and diffusion tensor imaging in grading gliomas, predicting tumour cell proliferation and IDH-1 gene mutation status [J]. J Neurooncol, 2019, 141(1): 195－203.
[22] Goyal A, Yolcu Y U, Goyal A, et al. The T2-FLAIR-mismatch sign as an imaging biomarker for IDH and 1p/19q status in diffuse low-grade gliomas: a systematic review with a Bayesian approach to evaluation of diagnostic test performance [J]. Neurosurg Focus, 2019, 47(6): E13.
[23] Broen M P G, Smits M, Wijnenga M M J, et al. The T2-FLAIR mismatch sign as an imaging marker for non-enhancing IDH-mutant, 1p/19q-intact lower-grade glioma: a validation study [J]. Neuro Oncol, 2018, 20(10): 1393－1399.
[24] Jansen N L, Schwartz C, Graute V, et al. Prediction of oligodendroglial histology and LOH 1p/19q using dynamic [¹⁸F]FET-PET imaging in intracranial WHO grade Ⅱ and Ⅲ gliomas [J]. Neuro Oncol, 2012, 14(12): 1473－1480.
[25] Castello A, Riva M, Fernandes B, et al. The role of ¹¹C-methionine PET in patients with negative diffusion-weighted magnetic resonance imaging: correlation with histology and molecular biomarkers in operated gliomas [J]. Nucl Med Commun, 2020, 41(7): 696－705.
[26] Saito T, Maruyama T, Muragaki Y, et al. ¹¹C-methionine uptake correlates with combined 1p and 19q loss of heterozygosity in oligodendroglial tumors [J]. AJNR Am J Neuroradiol, 2013, 34(1): 85－91.

¹¹C-MET PET/CT筛查幕上较低级别胶质瘤IDH和1p/19q分子分型的应用价值

Application of ¹¹C-MET PET/CT in screening isocitric dehydrogenase and 1p/19q status in supratentorial lower-grade gliomas

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