Institute of Neuroscience and Medicine (INM-3,-4,-5), Forschungszentrum Jülich, Jülich, Germany.
J Nucl Med. 2013 Dec;54(12):2046-54. doi: 10.2967/jnumed.113.123836. Epub 2013 Oct 24.
In patients with low-grade glioma (LGG) of World Health Organization (WHO) grade II, early detection of progression to WHO grade III or IV is of high clinical importance because the initiation of a specific treatment depends mainly on the WHO grade. In a significant number of patients with LGG, however, information on tumor activity and malignant progression cannot be obtained on the basis of clinical or conventional MR imaging findings only. We here investigated the potential of O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET to noninvasively detect malignant progression in patients with LGG.
Twenty-seven patients (mean age ± SD, 44 ± 15 y) with histologically proven LGG (WHO grade II) were investigated longitudinally twice using dynamic (18)F-FET PET and routine MR imaging. Initially, MR imaging and PET scans were performed, and diagnosis was confirmed on the basis of biopsy. Subsequently, PET scans were obtained when clinical findings or contrast-enhanced MR imaging suggested malignant progression. Maximum and mean tumor-to-brain ratios (20-40 min after injection) (TBRmax and TBRmean, respectively) of (18)F-FET uptake as well as tracer uptake kinetics (i.e., time to peak [TTP] and patterns of the time-activity curves) were determined. The diagnostic accuracy of imaging parameters for the detection of malignant progression was evaluated by receiver-operating-characteristic analyses and by Fisher exact test for 2 × 2 contingency tables.
In patients with histologically proven malignant progression toward WHO grade III or IV (n = 18), TBRmax and TBRmean increased significantly, compared with baseline (TBRmax, 3.8 ± 1.0 vs. 2.4 ± 1.0; TBRmean, 2.2 ± 0.3 vs. 1.6 ± 0.6; both P < 0.001), whereas TTP decreased significantly (median TTP, 35 vs. 23 min; P < 0.001). Furthermore, time-activity curve patterns changed significantly in 10 of 18 patients (P < 0.001). The combined analysis of (18)F-FET PET parameters (i.e., changes of TBRmax, TTP, or time-activity curve pattern) yielded a significantly higher diagnostic accuracy for the detection of malignant progression than changes of contrast enhancement in MR imaging (accuracy, 81% vs. 63%; P = 0.003).
Both tumor-to-brain ratio and kinetic parameters of (18)F-FET PET uptake provide valuable diagnostic information for the noninvasive detection of malignant progression of LGG. Thus, repeated (18)F-FET PET may be helpful for further treatment decisions.
在低级别胶质瘤（LGG）患者中，尽早发现进展为世界卫生组织（WHO）III 级或 IV 级是非常重要的，因为特定治疗的开始主要取决于 WHO 分级。然而，在相当数量的 LGG 患者中，仅基于临床或常规磁共振成像（MRI）发现，无法获得肿瘤活性和恶性进展的信息。我们在此研究了 O-（2-（18）F-氟乙基）-L-酪氨酸（18F-FET）PET 非侵入性检测 LGG 患者恶性进展的潜力。
27 名患者（平均年龄±标准差，44±15 岁）经组织学证实患有 LGG（WHO 分级 II），使用动态 18F-FET PET 和常规 MRI 进行了两次纵向研究。最初，进行 MRI 扫描和 PET 扫描，然后根据活检结果进行诊断。随后，当临床发现或对比增强 MRI 提示恶性进展时，进行 PET 扫描。确定 18F-FET 摄取的最大和平均肿瘤与脑比值（注射后 20-40 分钟）（TBRmax 和 TBRmean）以及示踪剂摄取动力学（即达峰时间[TTP]和时间-活性曲线模式）。通过接收者操作特征分析和 Fisher 确切检验对 2×2 列联表评估成像参数检测恶性进展的诊断准确性。
在组织学证实向 WHO 分级 III 或 IV 恶性进展的患者中（n=18），与基线相比，TBRmax 和 TBRmean 显著增加（TBRmax，3.8±1.0 比 2.4±1.0；TBRmean，2.2±0.3 比 1.6±0.6；均 P<0.001），而 TTP 显著降低（中位数 TTP，35 比 23 分钟；P<0.001）。此外，18 例患者中有 10 例（P<0.001）的时间-活性曲线模式发生显著变化。18F-FET PET 参数（即 TBRmax、TTP 或时间-活性曲线模式的变化）的联合分析对恶性进展的检测具有显著更高的诊断准确性，高于 MRI 对比增强的变化（准确性，81%比 63%；P=0.003）。
18F-FET 摄取的肿瘤与脑比值和动力学参数均为 LGG 恶性进展的非侵入性检测提供了有价值的诊断信息。因此，重复 18F-FET PET 检查可能有助于进一步的治疗决策。
