TSPO PET signal using [18F]GE180 is associated with survival in recurrent gliomas

Abstract

Purpose Glioma patients, especially recurrent glioma, suffer from a poor prognosis. While advances to classify glioma on a molecular level improved prognostication at initial diagnosis, markers to prognosticate survival in the recurrent situation are still needed. As 18 kDa translocator protein (TSPO) was previously reported to be associated with aggressive histopathological glioma features, we correlated the TSPO positron emission tomography (PET) signal using [18F]GE180 in a large cohort of recurrent glioma patients with their clinical outcome. Methods In patients with [18F]GE180 PET at glioma recurrence, [18F]GE180 PET parameters (e.g., SUVmax) as well as other imaging features (e.g., MRI volume, [18F]FET PET parameters when available) were evaluated together with patient characteristics (age, sex, Karnofsky-Performance score) and neuropathological features (e.g. WHO 2021 grade, IDH-mutation status). Uni- and multivariate Cox regression and Kaplan–Meier survival analyses were performed to identify prognostic factors for post-recurrence survival (PRS) and time to treatment failure (TTF). Results Eighty-eight consecutive patients were evaluated. TSPO tracer uptake correlated with tumor grade at recurrence (p < 0.05), with no significant differences in IDH-wild-type versus IDH-mutant tumors. Within the subgroup of IDH-mutant glioma (n = 46), patients with low SUVmax (median split, ≤ 1.60) had a significantly longer PRS (median 41.6 vs. 25.3 months, p = 0.031) and TTF (32.2 vs 8.7 months, p = 0.001). Also among IDH-wild-type glioblastoma (n = 42), patients with low SUVmax (≤ 1.89) had a significantly longer PRS (median not reached vs 8.2 months, p = 0.002). SUVmax remained an independent prognostic factor for PRS in the multivariate analysis including CNS WHO 2021 grade, IDH status, and age. Tumor volume defined by [18F]FET PET or contrast-enhanced MRI correlated weakly with TSPO tracer uptake. Treatment regimen did not differ among the median split subgroups. Conclusion Our data suggest that TSPO PET using [18F]GE180 can help to prognosticate recurrent glioma patients even among homogeneous molecular subgroups and may therefore serve as valuable non-invasive biomarker for individualized patient management. Graphical abstract

Translocator protein (18kDA) (TSPO) marks mesenchymal glioblastoma cell populations characterized by elevated numbers of tumor-associated macrophages

“…For histopathological evaluation of TSPO as a PET imaging marker, we utilized IDH-wildtype glioblastoma (GBM) samples (n = 26) of our multidisciplinary prospective cohort [ 58 ]. All study patients underwent TSPO-PET imaging and targeted biopsy or resection for correlation of imaging with histological parameters (Fig.…”

“…We used 26 IDH-wildtype GBM (biopsies/resections) from our FOR2858 (German Research Foundation, DFG) TSPO-PET imaging study (Suppl. Table 2) [ 58 ], collected in the Center for Neurosurgery/Neuropathology/Department of Nuclear Medicine, University Hospital of Munich (LMU Munich, Munich Germany) in line with local ethics board approval (ethics board approval no. 18–783).…”

“…However, its expression is upregulated at sites of inflammation or neurodegeneration [ 53 ] and also in gliomas [ 14 , 71 , 79 ]. TSPO-PET imaging is a potential prognostic marker in patients suffering from diffuse gliomas [ 14 , 58 ]. It has been described to mark the tumor microenvironment (TME) with its myeloid compartment and to indicate therapy-induced changes during tumor progression [ 22 , 57 , 79 ].…”

Deciphering sources of PET signals in the tumor microenvironment of glioblastoma at cellular resolution

“…First, lacking specificity of TSPO-PET signals for TAMs in glioblastoma hampers the biomarker's application as a mere immune index. However, since TSPO-PET signals allow prognostication of overall survival 34 , TSPO-PET still adds valuable biomarker features to the toolbox of glioblastoma imaging assessments 35 . These quantitative TSPO-PET data even exceeded the prognostic value of gene expression levels 36 , which could be related to the direct quantification of TSPO receptor abundance instead of indirect mRNA measures.…”

Deciphering sources of PET signals in the tumor microenvironment of glioblastoma at cellular resolution

“…First, lacking specificity of TSPO-PET signals for TAMs in glioblastoma hampers the biomarker’s application as a mere immune index. However, since TSPO-PET signals are associated with survival times in patients with primary and recurrent glioma ( 38 , 39 ), TSPO-PET still adds valuable biomarker features to the toolbox of glioblastoma imaging assessments ( 40 ). These quantitative TSPO-PET data even exceeded the prognostic value of gene expression levels ( 41 ), which could be related to the direct quantification of TSPO receptor abundance instead of indirect mRNA measures.…”