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

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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.