UMR 1023, IMIV, Service Hospitalier Frédéric Joliot, CEA, Inserm, Université Paris Sud, CNRS, Université Paris-Saclay, Orsay, France.
NeuroSpin, CEA/Université Paris-Saclay, Gif sur Yvette, France.
Neuro Oncol. 2019 Jun 10;21(6):755-764. doi: 10.1093/neuonc/noz029.
Glioblastoma (GBM) is the most devastating brain tumor. Despite the use of multimodal treatments, most patients relapse, often due to the highly invasive nature of gliomas. However, the detection of glioma infiltration remains challenging. The aim of this study was to assess advanced PET and MRI techniques for visualizing biological activity and infiltration of the tumor.
Using multimodality imaging, we investigated [18F]DPA-714, a radiotracer targeting the 18 kDa translocator protein (TSPO), [18F]FET PET, non-Gaussian diffusion MRI (apparent diffusion coefficient, kurtosis), and the S-index, a composite diffusion metric, to detect tumor infiltration in a human invasive glioma model. In vivo imaging findings were confirmed by autoradiography and immunofluorescence.
Increased tumor-to-contralateral [18F]DPA-714 uptake ratios (1.49 ± 0.11) were found starting 7 weeks after glioma cell implantation. TSPO-PET allowed visualization of glioma infiltration into the contralateral hemisphere 2 weeks earlier compared with the clinically relevant biomarker for biological glioma activity [18F]FET. Diffusion-weighted imaging (DWI), in particular kurtosis, was more sensitive than standard T2-weighted MRI to detect differences between the glioma-bearing and the contralateral hemisphere at 5 weeks. Immunofluorescence data reflect in vivo findings. Interestingly, labeling for tumoral and stromal TSPO indicates a predominant expression of TSPO by tumor cells.
These results suggest that advanced PET and MRI methods, such as [18F]DPA-714 and DWI, may be superior to standard imaging methods to visualize glioma growth and infiltration at an early stage.
胶质母细胞瘤（GBM）是最具破坏性的脑肿瘤。尽管采用了多模态治疗，但大多数患者仍会复发，这通常是由于胶质瘤的高度侵袭性。然而，胶质瘤浸润的检测仍然具有挑战性。本研究旨在评估高级 PET 和 MRI 技术在可视化肿瘤的生物学活性和浸润方面的应用。
我们使用多模态成像技术，研究了靶向 18 kDa 转位蛋白（TSPO）的放射性示踪剂 [18F]DPA-714、[18F]FET PET、非高斯扩散 MRI（表观扩散系数、峰度）和 S 指数（一种复合扩散指标），以检测人类侵袭性脑胶质瘤模型中的肿瘤浸润。通过放射自显影和免疫荧光证实了体内成像结果。
在植入胶质母细胞瘤细胞后 7 周，发现肿瘤与对侧 [18F]DPA-714 摄取比值增加（1.49±0.11）。与生物胶质瘤活性的临床相关生物标志物 [18F]FET 相比，TSPO-PET 能够更早地显示出胶质瘤向对侧半球的浸润，提前 2 周。与标准 T2 加权 MRI 相比，扩散加权成像（DWI），特别是峰度，在 5 周时更能敏感地检测到肿瘤侧和对侧半球之间的差异。免疫荧光数据反映了体内发现。有趣的是，肿瘤和基质 TSPO 的标记表明 TSPO 主要由肿瘤细胞表达。
这些结果表明，高级 PET 和 MRI 方法，如 [18F]DPA-714 和 DWI，可能优于标准成像方法，能够更早地可视化胶质瘤的生长和浸润。
