背景:胶质瘤的特点是复发率高,而传统成像方法(包括磁共振成像,MRI)将复发与治疗相关的变化(TRC)区分开来较差。前列腺特异性膜抗原(PSMA)(US10815200B2,DeutschesKrebsforschunchszentrum,德国癌症研究中心)是在神经胶质瘤血管内皮中过表达的II型跨膜糖蛋白,它是成像和治疗的一个有前途的目标。
目的:该研究旨在评估PSMA正电子发射断层扫描/磁共振(PET/MR)在诊断胶质瘤患者复发和预测预后方面的表现。
方法:前瞻性纳入接受18F-PSMA-1007PET/MR检查的疑似胶质瘤复发患者。从PSMAPET/MR中提取了病变的8个代谢参数和15个纹理特征。研究了PSMAPET/MR诊断胶质瘤复发的能力,并与常规MRI进行了比较。使用Cohenκ评分评估诊断一致性,并获得PSMAPET/MR的预测参数。采用Kaplan-Meier法和Cox比例风险模型分析无复发生存期(RFS)和总生存期(OS)。最后,免疫组织化学(IHC)分析PSMA的表达。
结果:评估了19例患者,平均年龄为48.11±15.72。从PET和T1加权对比增强(T1-CE)MR中提取的最大肿瘤-腮腺比率(TPRmax)和纹理特征显示复发和TRC之间存在差异(均p<0.05)。PSMAPET/MR和常规MRI在诊断复发方面具有相当的能力,特异性和PPV为100%。两种模式之间的观察者间一致性是公平的(κ=0.542,p=0.072)。代谢参数的最佳截止值,包括标准化的摄取价值(SUV,SUVmax,Suvmean,和SUVpeak)和预测复发的TPRmax分别为3.35、1.73、1.99和0.17,曲线下面积(AUC)范围为0.767至0.817(均p<0.05)。在4级胶质母细胞瘤(GBM)患者中,SUVmax,Suvmean,SUVpeak,TBRmax,TBRmean,和TPRmax显示AUC性能改善(0.833-0.867,p<0.05)。SUVmax患者,Suvmean,或SUVpeak超过临界值的RFS明显较短(均p<0.05)。此外,SUVmean患者,SUVpeak,或超过临界值的TPRmax具有显著较短的OS(所有p<0.05)。在所有GBM病例(n=6/6,100%)中,有10例(10/11,90.9%)患者中观察到神经胶质瘤血管内皮的PSMA表达。
结论:这项原始研究表明,通过提供出色的肿瘤背景比较,多参数PSMAPET/MR可用于识别神经胶质瘤(尤其是GBM)复发。肿瘤异质性,复发预测和预后信息,尽管与常规MRI相比,它并未改善诊断性能。需要进一步和更大的研究来定义其在这种情况下的潜在临床应用。
BACKGROUND: Glioma is characterized by a high recurrence rate, while the results of the traditional imaging methods (including magnetic resonance imaging, MRI) to distinguish recurrence from treatment-related changes (TRCs) are poor. Prostate-specific membrane antigen (PSMA) (US10815200B2, Deutsches Krebsforschungszentrum, German Cancer Research Center) is a type II transmembrane glycoprotein overexpressed in glioma vascular endothelium, and it is a promising target for imaging and therapy.
OBJECTIVE: The study aimed to assess the performance of PSMA positron emission tomography/ magnetic resonance (PET/MR) for diagnosing recurrence and predicting prognosis in glioma patients.
METHODS: Patients suspected of glioma recurrence who underwent 18F-PSMA-1007 PET/MR were prospectively enrolled. Eight metabolic parameters and fifteen texture features of the lesion were extracted from PSMA PET/MR. The ability of PSMA PET/MR to diagnose glioma recurrence was investigated and compared with conventional MRI. The diagnostic agreement was assessed using Cohen κ scores and the predictive parameters of PSMA PET/MR were obtained. Kaplan-Meier method and Cox proportional hazard model were used to analyze recurrence- free survival (RFS) and overall survival (OS). Finally, the expression of PSMA was analyzed by immunohistochemistry (IHC).
RESULTS: Nineteen patients with a mean age of 48.11±15.72 were assessed. The maximum tumorto- parotid ratio (TPRmax) and texture features extracted from PET and T1-weighted contrast enhancement (T1-CE) MR showed differences between recurrence and TRCs (all p <0.05). PSMA PET/MR and conventional MRI exhibited comparable power in diagnosing recurrence with specificity and PPV of 100%. The interobserver concordance was fair between the two modalities (κ = 0.542, p = 0.072). The optimal cutoffs of metabolic parameters, including standardized uptake value (SUV, SUVmax, SUVmean, and SUVpeak) and TPRmax for predicting recurrence were 3.35, 1.73, 1.99, and 0.17 respectively, with the area under the curve (AUC) ranging from 0.767 to 0.817 (all p <0.05). In grade 4 glioblastoma (GBM) patients, SUVmax, SUVmean, SUVpeak, TBRmax, TBRmean, and TPRmax showed improved performance of AUC (0.833-0.867, p <0.05). Patients with SUVmax, SUVmean, or SUVpeak more than the cutoff value had significantly shorter RFS (all p <0.05). In addition, patients with SUVmean, SUVpeak, or TPRmax more than the cutoff value had significantly shorter OS (all p <0.05). PSMA expression of glioma vascular endothelium was observed in ten (10/11, 90.9%) patients with moderate-to-high levels in all GBM cases (n = 6/6, 100%).
CONCLUSIONS: This primitive study shows multiparameter PSMA PET/MR to be useful in identifying glioma (especially GBM) recurrence by providing excellent tumor background comparison, tumor heterogeneity, recurrence prediction and prognosis information, although it did not improve the diagnostic performance compared to conventional MRI. Further and larger studies are required to define its potential clinical application in this setting.