Unterrainer M, Fleischmann D F, Vettermann F, Ruf V, Kaiser L, Nelwan D, Lindner S, Brendel M, Wenter V, Stöcklein S, Herms J, Milenkovic V M, Rupprecht R, Tonn J C, Belka C, Bartenstein P, Niyazi M, Albert N L
Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany.
German Cancer Consortium (DKTK), Partner Site Munich, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Eur J Nucl Med Mol Imaging. 2020 Jun;47(6):1368-1380. doi: 10.1007/s00259-019-04491-5. Epub 2019 Sep 5.
The 18-kDa translocator protein (TSPO) is overexpressed in brain tumours and represents an interesting target for glioma imaging. F-GE-180, a novel TSPO ligand, has shown improved binding affinity and a high target-to-background contrast in patients with glioblastoma. However, the association of uptake characteristics on TSPO PET using F-GE-180 with the histological WHO grade and molecular genetic features so far remains unknown and was evaluated in the current study.
Fifty-eight patients with histologically validated glioma at initial diagnosis or recurrence were included. All patients underwent F-GE-180 PET, and the maximal and mean tumour-to-background ratios (TBR, TBR) as well as the PET volume were assessed. On MRI, presence/absence of contrast enhancement was evaluated. Imaging characteristics were correlated with neuropathological parameters (i.e. WHO grade, isocitrate dehydrogenase (IDH) mutation, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and telomerase reverse transcriptase (TERT) promoter mutation).
Six of 58 patients presented with WHO grade II, 16/58 grade III and 36/58 grade IV gliomas. An (IDH) mutation was found in 19/58 cases, and 39/58 were classified as IDH-wild type. High F-GE-180-uptake was observed in all but 4 cases (being WHO grade II glioma, IDH-mutant). A high association of F-GE-180-uptake and WHO grades was seen: WHO grade IV gliomas showed the highest uptake intensity compared with grades III and II gliomas (median TBR 5.15 (2.59-8.95) vs. 3.63 (1.85-7.64) vs. 1.63 (1.50-3.43), p < 0.001); this association with WHO grades persisted within the IDH-wild-type and IDH-mutant subgroup analyses (p < 0.05). Uptake intensity was also associated with the IDH mutational status with a trend towards higher F-GE-180-uptake in IDH-wild-type gliomas in the overall group (median TBR 4.67 (1.56-8.95) vs. 3.60 (1.50-7.64), p = 0.083); however, within each WHO grade, no differences were found (e.g. median TBR in WHO grade III glioma 4.05 (1.85-5.39) vs. 3.36 (2.32-7.64), p = 1.000). No association was found between uptake intensity and MGMT or TERT (p > 0.05 each).
Uptake characteristics on F-GE-180 PET are highly associated with the histological WHO grades, with the highest F-GE-180 uptake in WHO grade IV glioblastomas and a PET-positive rate of 100% among the investigated high-grade gliomas. Conversely, all TSPO-negative cases were WHO grade II gliomas. The observed association of F-GE-180 uptake and the IDH mutational status seems to be related to the high inter-correlation of the IDH mutational status and the WHO grades.
18 kDa转运蛋白（TSPO）在脑肿瘤中过表达，是胶质瘤成像的一个有吸引力的靶点。新型TSPO配体F-GE-180在胶质母细胞瘤患者中显示出更高的结合亲和力和高靶本底对比度。然而，迄今为止，使用F-GE-180进行的TSPO PET摄取特征与世界卫生组织（WHO）组织学分级和分子遗传学特征之间的关联尚不清楚，本研究对此进行了评估。
纳入58例初诊或复发时经组织学证实为胶质瘤的患者。所有患者均接受F-GE-180 PET检查，并评估最大和平均肿瘤与本底比值（TBR、TBR）以及PET体积。在MRI上，评估有无对比增强。将成像特征与神经病理学参数（即WHO分级、异柠檬酸脱氢酶（IDH）突变、O-6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化和端粒酶逆转录酶（TERT）启动子突变）进行关联分析。
58例患者中，6例为WHO二级胶质瘤，16/58例为三级，36/例为四级。19/58例患者检测到（IDH）突变，39/58例为IDH野生型。除4例（WHO二级胶质瘤，IDH突变型）外，所有患者均观察到F-GE-180高摄取。F-GE-180摄取与WHO分级高度相关：与三级和二级胶质瘤相比，四级胶质瘤的摄取强度最高（中位TBR 5.15（范围2.59-8.95）vs. 3.63（范围1.85-7.64）vs. 1.63（范围1.50-3.43），p < 0.001）；在IDH野生型和IDH突变型亚组分析中，这种与WHO分级的关联依然存在（p < 0.05）。摄取强度也与IDH突变状态相关，总体上IDH野生型胶质瘤中F-GE-180摄取有升高趋势（中位TBR 4.67（范围1.56-8.95）vs. 3.60（范围1.50-7.64），p = 0.083）；然而，在每个WHO分级内，未发现差异（如WHO三级胶质瘤的中位TBR 4.05（范围1.85-5.39）vs. 3.36（范围2.32-7.64），p = 1.000）。摄取强度与MGMT或TERT之间未发现关联（p均> 0.05）。
F-GE-180 PET摄取特征与WHO组织学分级高度相关，在四级胶质母细胞瘤中F-GE-180摄取最高，在研究的高级别胶质瘤中PET阳性率为100%。相反，所有TSPO阴性病例均为WHO二级胶质瘤。观察到的F-GE-180摄取与IDH突变状态的关联似乎与IDH突变状态和WHO分级之间的高度相关性有关。
