分子标记在分类、治疗和预测中枢神经系统肿瘤的预后中变得越来越重要。异柠檬酸脱氢酶（IDH）是葡萄糖和氨基酸代谢的关键调节器。我们的目标是利用细胞内摄取（CU）特征研究胶质瘤的代谢重编程，评估氧-（2-18F-氟乙基）-l-酪氨酸（FET）PET在IDH基因分型中的诊断潜力。方法：2017年至2022年间，经确认为胶质瘤的患者进行术前静态18F-FET PET检查。利用U-Net神经架构和等值线法自动分割代谢性肿瘤体积（MTV），60%-100%摄取MTV（MTV60），T2加权和对比增强病灶体积。利用Dice系数确定体积交叉点。计算代谢性定义区域（18F-FET摄取的中心[80%-100%]和外围[60%-75%]区域）的摄取特征。CU比率定义为外围和中心区域之间的分数。计算平均靶-背景比。使用参数统计和非参数统计进行比较。接受者操作特征曲线，回归和相关性进行统计分析。结果：共评估了52名参与者（男性27名，女性25名；平均年龄±标准差，51±16岁）。MTV60大于对比增强病灶体积且与之不同（P=0.046）。IDH突变肿瘤与IDH野生型肿瘤相比，CU体积比率和SUV CU比率均较高（P<0.05）。体积CU比率在IDH基因型的诊断表现上具有良好的性能（曲线下面积[AUC]，0.88；P<0.001），在大于5.49时（敏感度86%，特异度90%），因为IDH突变肿瘤的外围代谢区域大于IDH野生型肿瘤（P=0.045）。MTV60和MTV对IDH分类不适用（P>0.05）。SUV CU比率（AUC，0.72；P=0.005）和靶-背景比（AUC，0.68；P=0.016）的诊断表现一般，低于体积CU比率。此外，还评估了氨基酸PET对1p和19q染色体杂合性丧失（AUC，0.75；P=0.019）、MGMT启动子甲基化（AUC，0.70；P=0.011）和ATRX缺失（AUC，0.73；P=0.004）的分类。结论：我们提出将参数化的18F-FET PET作为无创代谢生物标记物评估CU特征的方法，该方法能够以优秀的诊断性能区分IDH基因型，在空间代谢异质性、线粒体三羧酸循环和基因组特征之间建立关键关联，对临床管理和中枢神经系统肿瘤患者的诊断工作具有重要意义。© 2023年核医学和分子影像学协会翻译

Molecular markers are of increasing importance for classifying, treating, and determining the prognosis for central nervous system tumors. Isocitrate dehydrogenase (IDH) is a critical regulator of glucose and amino acid metabolism. Our objective was to investigate metabolic reprogramming of glioma using compartmental uptake (CU) characteristics in O-(2-18F-fluoroethyl)-l-tyrosine (FET) PET and to evaluate its diagnostic potential for IDH genotyping. Methods: Between 2017 and 2022, patients with confirmed glioma were preoperatively investigated using static 18F-FET PET. Metabolic tumor volume (MTV), MTV for 60%-100% uptake (MTV60), and T2-weighted and contrast-enhancing lesion volumes were automatically segmented using U-Net neural architecture and isocontouring. Volume intersections were determined using the Dice coefficient. Uptake characteristics were determined for metabolically defined compartments (central [80%-100%] and peripheral [60%-75%] areas of 18F-FET uptake). CU ratio was defined as the fraction between the peripheral and central compartments. Mean target-to-background ratio was calculated. Comparisons were performed using parametric and nonparametric tests. Receiver-operating-characteristic curves, regression, and correlation were used for statistical analysis. Results: In total, 52 participants (male, 27, female, 25; mean age ± SD, 51 ± 16 y) were evaluated. MTV60 was greater and distinct from contrast-enhancing lesion volume (P = 0.046). IDH-mutated tumors presented a greater volumetric CU ratio and SUV CU ratio than IDH wild-type tumors (P < 0.05). Volumetric CU ratio determined IDH genotype with excellent diagnostic performance (area under the curve [AUC], 0.88; P < 0.001) at more than 5.49 (sensitivity, 86%, specificity, 90%), because IDH-mutated tumors presented a greater peripheral metabolic compartment than IDH wild-type tumors (P = 0.045). MTV60 and MTV were not suitable for IDH classification (P > 0.05). SUV CU ratio (AUC, 0.72; P = 0.005) and target-to-background ratio (AUC, 0.68; P = 0.016) achieved modest diagnostic performance-inferior to the volumetric CU ratio. Furthermore, the classification of loss of heterozygosity of chromosomes 1p and 19q (AUC, 0.75; P = 0.019), MGMT promoter methylation (AUC, 0.70; P = 0.011), and ATRX loss (AUC, 0.73; P = 0.004) by amino acid PET was evaluated. Conclusion: We proposed parametric 18F-FET PET as a noninvasive metabolic biomarker for the evaluation of CU characteristics, which differentiated IDH genotype with excellent diagnostic performance, establishing a critical association between spatial metabolic heterogeneity, mitochondrial tricarboxylic acid cycle, and genomic features with critical implications for clinical management and the diagnostic workup of patients with central nervous system cancer.© 2023 by the Society of Nuclear Medicine and Molecular Imaging.