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

神经胶质瘤中的 TSPO PET 标记作为人脑的诊断标记

• 批准号: 421887978
• 负责人: Professorin Dr. Nathalie Albert
• 金额: --
• 依托单位: Klinik und Poliklinik für Nuklearmedizin
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/421887978?language=en
• 关键词: TSPO; PET; labeling; gliomas; diagnostic

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.

TSPO在原发性脑肿瘤中过表达，并已显示与肿瘤细胞的恶性程度相关。先前的工作已经表明，胶质瘤的PET信号在TSPO PET和氨基酸PET（[18 F]FET）中是不同的，并且也不同于MRI中的对比增强。到目前为止，尚不清楚不同的成像方式反映了哪些肿瘤特征，以及这是否对患者的临床结果和预后产生影响。该项目旨在与项目A2和A3一起描绘人脑中TSPO过表达的神经生物学基础。此外，它将研究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相关。我们在工作包1中计划在立体定向活检或手术切除之前对三个患者人群（疑似胶质母细胞瘤、MRI上无对比增强的胶质瘤和进行性/复发性胶质瘤）进行前瞻性临床评价。所有患者在神经外科干预前将接受高亲和力TSPO配体[18 F]GE-180的PET成像、FET-PET和MRI。将使用图像引导神经导航系统进行肿瘤切除和连续立体定向活检。组织样本的精确定位将被分配给PET和MRI数据，这使得PET信息与组织病理学发现和途径分析之间具有精确的空间相关性（项目A2/A3）。研究的招募期为18个月，随访期为另外18个月。在资助期的前半部分，工作包2的主要目标将是开发一种易于操作的软件工具，用于增加的氨基酸转运、FET动力学差异、[18 F]GE-180积累和血脑屏障破坏之间的重叠区、增加的氨基酸转运和小胶质细胞活化的体素可视化。将在工作包1、3和项目A2（精细成像、临床数据和组织学相关性）中采集，为应用自动化图像分析和机器学习提供了独特的机会。该工作包在资助期后半期的目标是在图像特征与局部复发的位置和时间以及最终的总体生存率之间建立联系。第二套工作包的一部分还将是在里根斯堡大学医院建立TSPO PET成像，第三套工作包涉及建立一个临床数据库，以便系统地整合临床、成像和神经病理学数据。从临床检查中检索到的所有数据，特别是从疾病过程中的临床随访、初始和随访成像和神经病理学分析（每份样本的组织学和分子特征）中检索到的所有数据将完全登记在专用数据库中，以供进一步分析。