TSPO PET labeling in gliomas as a diagnostic marker in the human brain

TSPO在原发性脑肿瘤中过表达，并已被证明与肿瘤细胞的恶性相关。以往的研究表明，胶质瘤的PET信号在TSPO PET和氨基酸PET （[18F]FET）中是不同的，也不同于MRI的对比增强。目前尚不清楚不同的影像学方式反映了哪些肿瘤特征，以及这是否对患者的临床结局和预后有影响。本项目旨在与A2和A3项目一起描述人脑中TSPO过表达的神经生物学基础。此外，该研究还将探讨TSPO PET和FET PET联合成像是否比结构MRI更可靠地描绘肿瘤边界，以及TSPO PET信号增加是否与异质性胶质瘤的侵袭性肿瘤特征有关。我们计划在工作包1中对三个患者群体（疑似胶质母细胞瘤、MRI未增强的胶质瘤和进展/复发性胶质瘤）进行前瞻性临床评估，然后进行立体定向活检或手术切除。所有患者在神经外科干预前都将接受高亲和力TSPO配体[18F]GE-180、FET-PET和MRI的PET成像。肿瘤切除和连续立体定向活检将使用图像引导神经导航系统进行。组织样本的精确定位将分配给PET和MRI数据，这使得PET信息与组织病理学发现和通路分析的精确空间相关性（项目A2/A3）。招募期为18个月，随访期为18个月。在资助期的前半段，工作包2的主要目标将是开发一种易于操作的软件工具，用于增加的氨基酸运输的体向可视化，fet动力学的差异，[18F]GE-180积累和血脑屏障破坏之间的重叠区域，增加的氨基酸运输和小胶质细胞激活。扩展的数据集将在工作包1,3和项目A2（详细的成像，临床数据和组织学相关性）中获得，为应用自动图像分析和机器学习提供了独特的机会。在资助期的后半段，该工作包的目标是建立图像特征与局部复发的位置和时间之间的联系，并最终建立整体生存。工作包2的一部分还将是在雷根斯堡大学医院建立TSPO PET成像。工作包3涉及建立临床数据库，以便系统整合临床、影像学和神经病理学数据。所有从临床检查中检索到的数据，特别是从疾病过程中的临床随访、初始和随访成像以及神经病理分析（每个样本的组织学和分子谱）中检索到的数据将完全登记在专用数据库中，以供进一步分析。

TSPO is overexpressed in primary brain tumors and has been shown to correlate with the malignancy of the tumor cells. Previous work has shown that the PET signal of gliomas in TSPO PET and amino acid PET ([18F]FET) are different and also differ from contrast enhancement in MRI. So far, it is not known which tumor features are reflected by the different imaging modalities and whether this has an impact on the clinical outcome and prognosis of patients. This project aims to delineate the neurobiology underlying TSPO overexpression in the human brain together with projects A2 and A3. Moreover, it will investigate whether combined TSPO PET and FET PET imaging can delineate tumor borders more reliably than structural MRI and whether an increased TSPO PET signal is associated with aggressive tumor features in heterogeneous gliomas. We plan in work package 1 a prospective clinical evaluation of three patient populations (suspected glioblastoma, glioma without contrast enhancement on MRI and progressive/recurrent glioma) prior to stereotactic biopsy or surgical resection. All patients will undergo PET imaging with the high affinity TSPO ligand [18F]GE-180, FET-PET and MRI prior to the neurosurgical intervention. Tumor resection and serial stereotactic biopsies will be performed using an image guided neuronavigation system. The exact localizations of tissue samples will be assigned to PET and MRI data, which enables a precise spatial correlation of PET information with histopathological findings and pathway analysis (project A2/A3). Recruitment phase of the study will be 18 months with follow-up of another 18 months. In the first half of the funding period the major aim of work package 2 will be the development of an easy to handle software tool for the voxelwise visualization of increased amino acid transport, differences in FET-kinetics, [18F]GE-180 accumulation and overlap zones between blood-brain-barrier disruption, increased amino acid transport and microglia activation.The extended set of data, which will be acquired within work package 1, 3 and project A2 (elaborated imaging, clinical data and histological correlation), provides a unique opportunity to apply automated image analysis and machine learning. The goal of this work package in the second half of the funding period is to establish a link between image features with the location and time of local relapse and ultimately the overall survival. Part of work package 2 will also be the establishment of TSPO PET imaging at the University Hospital Regensburg.Work package 3 deals with the set up of a clinical data base for systematic integration of clinical, imaging and neuropathological data. All data retrieved from clinical workup, in particular from clinical follow-up during the disease course, initial and follow-up imaging and neuropathological analysis (histology and molecular profile of each sample) will be fully registered in the dedicated databank for further analysis.