Department of Neuropathology, Institute of Pathology, Technische Universität München, Trogerstraße 18, 81675, Munich, Germany.
Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany.
Eur J Nucl Med Mol Imaging. 2019 Sep;46(10):2163-2168. doi: 10.1007/s00259-019-04407-3. Epub 2019 Jul 9.
To investigate the in vivo correlation between F-fluoroethyl-tyrosine (F-FET) uptake and amino acid transporter expression and vascularization in treatment-naive glioblastomas.
A total of 43 stereotactic biopsies were obtained from 13 patients with suspected glioblastoma prior to therapy. All patients underwent a dynamic F-FET PET/MRI scan before biopsy. Immunohistochemistry was performed using antibodies against SLC7A5 (amino acid transporter), MIB-1 (Ki67, proliferation), CD31 (vascularization) and CA-IX (hypoxia). The intensity of staining was correlated with F-FET uptake and the dynamic F-FET uptake slope at the biopsy target point.
In all patients, the final diagnosis was IDH-wildtype glioblastoma, WHO grade IV. Static F-FET uptake was significantly correlated with SLC7A5 staining (r = 0.494, p = 0.001). While the dynamic F-FET uptake slope did not show a significant correlation with amino acid transporter expression, it was significantly correlated with the number of CD31-positive vessels (r = -0.350, p = 0.031), which is line with earlier results linking F-FET kinetics with vascularization and perfusion. Besides, static F-FET uptake also showed correlations with CA-IX staining (r = 0.394, p = 0.009) and CD31 positivity (r = 0.410, p = 0.006). While the correlation between static F-FET uptake and SLC7A5 staining was confirmed as significant in multivariate analysis, this was not the case for the correlation with CD31 positivity, most likely because of the lower effect size and the relatively low number of samples. No significant correlation between F-FET uptake and Ki67 proliferation index was observed in our cohort.
Our results support the findings of preclinical studies suggesting that specific F-FET uptake in glioblastomas is mediated by amino acid transporters. As proposed previously, dynamic F-FET parameters might be more influenced by perfusion and therefore related to properties of the tumour neovascularization.
研究治疗前初诊脑胶质瘤中 F-氟乙基酪氨酸（F-FET）摄取与氨基酸转运体表达和血管生成的体内相关性。
13 名疑似脑胶质瘤患者在治疗前共进行了 43 例立体定向活检。所有患者在活检前均进行了 F-FET 动态 PET/MRI 扫描。使用针对 SLC7A5（氨基酸转运体）、MIB-1（Ki67，增殖）、CD31（血管生成）和 CA-IX（缺氧）的抗体进行免疫组织化学染色。染色强度与活检靶点处 F-FET 摄取和 F-FET 摄取斜率的动态变化相关。
所有患者的最终诊断均为 IDH 野生型脑胶质瘤，WHO 分级 IV 级。静态 F-FET 摄取与 SLC7A5 染色呈显著正相关（r=0.494，p=0.001）。虽然动态 F-FET 摄取斜率与氨基酸转运体表达无显著相关性，但与 CD31 阳性血管数呈显著负相关（r=-0.350，p=0.031），这与之前将 F-FET 动力学与血管生成和灌注联系起来的结果一致。此外，静态 F-FET 摄取还与 CA-IX 染色（r=0.394，p=0.009）和 CD31 阳性表达（r=0.410，p=0.006）相关。在多变量分析中，静态 F-FET 摄取与 SLC7A5 染色的相关性被证实具有统计学意义，而与 CD31 阳性表达的相关性则不具有统计学意义，这很可能是由于效应量较小且样本数量相对较少。在本研究队列中，未观察到 F-FET 摄取与 Ki67 增殖指数之间存在显著相关性。
本研究结果支持了之前的临床前研究结果，表明脑胶质瘤中特定的 F-FET 摄取是由氨基酸转运体介导的。如前所述，动态 F-FET 参数可能更受灌注的影响，因此与肿瘤新生血管化的特性相关。
