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(1) Background: Clinical aspects like sex, age, Karnofsky Performance Scale (KPS) and psychosocial distress can affect the health-related quality of life (HR-QoL) and treatment satisfaction of patients with malignant isocitrate dehydrogenase wild-type (IDHwt) gliomas and caregivers. (2) Methods: We prospectively investigated the HR-QoL and patient/caregiver treatment satisfaction in a cross-sectional study with univariable and multiple regression analyses. Questionnaires were applied to investigate the HR-QoL (EORTC QLQ-C30, QLQ-BN20) and treatment satisfaction (EORTC PATSAT-C33). (3) Results: A cohort of 61 patients was investigated. A higher KPS was significantly associated with a better HR-QoL regarding the functional scales of the EORTC QLQ-C30 (p < 0.004) and a lower symptom burden regarding the EORTC QLQ-BN20 (p < 0.001). The patient treatment satisfaction was significantly poorer in the patients older than 60 years in the domain of family involvement (p = 0.010). None of the investigated aspects showed a significant impact on the treatment satisfaction of caregivers. (4) Conclusions: We demonstrated that in patients with IDHwt gliomas, the KPS was the most important predictor for a better HR-QoL in functional domains. Data on the HR-QoL and treatment satisfaction in patients with IDHwt gliomas and their caregivers are rare; therefore, further efforts should be made to improve supportive care in this highly distressed cohort.

Background: The translocator protein (TSPO) has been proven to have great potential as a target for the positron emission tomography (PET) imaging of glioblastoma. However, there is an ongoing debate about the potential various sources of the TSPO PET signal. This work investigates the impact of the inoculation-driven immune response on the PET signal in experimental orthotopic glioblastoma. Methods: Serial [18F]GE-180 and O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) PET scans were performed at day 7/8 and day 14/15 after the inoculation of GL261 mouse glioblastoma cells (n = 24) or saline (sham, n = 6) into the right striatum of immunocompetent C57BL/6 mice. An additional n = 25 sham mice underwent [18F]GE-180 PET and/or autoradiography (ARG) at days 7, 14, 21, 28, 35, 50 and 90 in order to monitor potential reactive processes that were solely related to the inoculation procedure. In vivo imaging results were directly compared to tissue-based analyses including ARG and immunohistochemistry. Results: We found that the inoculation process represents an immunogenic event, which significantly contributes to TSPO radioligand uptake. [18F]GE-180 uptake in GL261-bearing mice surpassed [18F]FET uptake both in the extent and the intensity, e.g., mean target-to-background ratio (TBRmean) in PET at day 7/8: 1.22 for [18F]GE-180 vs. 1.04 for [18F]FET, p < 0.001. Sham mice showed increased [18F]GE-180 uptake at the inoculation channel, which, however, continuously decreased over time (e.g., TBRmean in PET: 1.20 at day 7 vs. 1.09 at day 35, p = 0.04). At the inoculation channel, the percentage of TSPO/IBA1 co-staining decreased, whereas TSPO/GFAP (glial fibrillary acidic protein) co-staining increased over time (p < 0.001). Conclusion: We identify the inoculation-driven immune response to be a relevant contributor to the PET signal and add a new aspect to consider for planning PET imaging studies in orthotopic glioblastoma models.

Conventional 2D cultures are commonly used in cancer research though they come with limitations such as the lack of microenvironment or reduced cell heterogeneity. In this study, we investigated in what respect a scaffold-based (Matrigel™) 3D culture technique can ameliorate the limitations of 2D cultures. NGS-based bulk and single-cell sequencing of matched pairs of 2D and 3D models showed an altered transcription of key immune regulatory genes in around 36% of 3D models, indicating the reoccurrence of an immune suppressive phenotype. Changes included the presentation of different HLA surface molecules as well as cellular stressors. We also investigated the 3D tumor organoids in a co-culture setting with tumor-infiltrating lymphocytes (TILs). Of note, lymphocyte-mediated cell killing appeared less effective in clearing 3D models than their 2D counterparts. IFN-γ release, as well as live cell staining and proliferation analysis, pointed toward an elevated resistance of 3D models. In conclusion, we found that the scaffold-based (Matrigel™) 3D culture technique affects the transcriptional profile in a subset of GBM models. Thus, these models allow for depicting clinically relevant aspects of tumor-immune interaction, with the potential to explore immunotherapeutic approaches in an easily accessible in vitro system.

The 18 kDa translocator protein (TSPO) is increasingly recognized as an interesting target for the imaging of glioblastoma (GBM). Here, we investigated TSPO PET imaging and autoradiography in the frequently used GL261 glioblastoma mouse model and aimed to generate insights into the temporal evolution of TSPO radioligand uptake in glioblastoma in a preclinical setting. We performed a longitudinal [18F]GE-180 PET imaging study from day 4 to 14 post inoculation in the orthotopic syngeneic GL261 GBM mouse model (n = 21 GBM mice, n = 3 sham mice). Contrast-enhanced computed tomography (CT) was performed at the day of the final PET scan (±1 day). [18F]GE-180 autoradiography was performed on day 7, 11 and 14 (ex vivo: n = 13 GBM mice, n = 1 sham mouse; in vitro: n = 21 GBM mice; n = 2 sham mice). Brain sections were also used for hematoxylin and eosin (H&E) staining and TSPO immunohistochemistry. [18F]GE-180 uptake in PET was elevated at the site of inoculation in GBM mice as compared to sham mice at day 11 and later (at day 14, TBRmax +27% compared to sham mice, p = 0.001). In GBM mice, [18F]GE-180 uptake continuously increased over time, e.g., at day 11, mean TBRmax +16% compared to day 4, p = 0.011. [18F]GE-180 uptake as depicted by PET was in all mice co-localized with contrast-enhancement in CT and tissue-based findings. [18F]GE-180 ex vivo and in vitro autoradiography showed highly congruent tracer distribution (r = 0.99, n = 13, p < 0.001). In conclusion, [18F]GE-180 PET imaging facilitates non-invasive in vivo monitoring of TSPO expression in the GL261 GBM mouse model. [18F]GE-180 in vitro autoradiography is a convenient surrogate for ex vivo autoradiography, allowing for straightforward identification of suitable models and scan time-points on previously generated tissue sections.

Treatment of glioblastoma (GBM) consists of microsurgical resection followed by concomitant radiochemotherapy and adjuvant chemotherapy. The best outcome regarding progression free (PFS) and overall survival (OS) is achieved by maximal resection. The foundation of a specialized neuro-oncology care center (NOC) has enabled the implementation of a large technical portfolio including functional imaging, awake craniotomy, PET scanning, fluorescence-guided resection, and integrated postsurgical therapy. This study analyzed whether the technically improved neurosurgical treatment structure yields a higher rate of complete resection, thus ultimately improving patient outcome. Patients and methods: The study included 149 patients treated surgically for newly diagnosed GBM. The neurological performance score (NPS) and the Karnofsky performance score (KPS) were measured before and after resection. The extent of resection (EOR) was volumetrically quantified. Patients were stratified into two subcohorts: treated before (A) and after (B) the foundation of the Regensburg NOC. The EOR and the PFS and OS were evaluated. Results: Prognostic factors for PFS and OS were age, preoperative KPS, O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status, isocitrate dehydrogenase 1 (IDH1) mutation status and EOR. Patients with volumetrically defined complete resection had significantly better PFS (9.4 vs. 7.8 months; p = 0.042) and OS (18.4 vs. 14.5 months; p = 0.005) than patients with incomplete resection. The frequency of transient or permanent postoperative neurological deficits was not higher after complete resection in both subcohorts. The frequency of complete resection was significantly higher in subcohort B than in subcohort A (68.2% vs. 34.8%; p = 0.007). Accordingly, subcohort B showed significantly longer PFS (8.6 vs. 7.5 months; p = 0.010) and OS (18.7 vs. 12.4 months; p = 0.001). Multivariate Cox regression analysis showed complete resection, age, preoperative KPS, and MGMT promoter status as independent prognostic factors for PFS and OS. Our data show a higher frequency of complete resection in patients with GBM after the establishment of a series of technical developments that resulted in significantly better PFS and OS without increasing surgery-related morbidity.

More than 40 human cases of severe encephalitis caused by Borna disease virus 1 (BoDV-1) have been reported to German health authorities. In an endemic region in southern Germany, we conducted the seroepidemiological BoSOT study (“BoDV-1 after solid-organ transplantation”) to assess whether there are undetected oligo- or asymptomatic courses of infection. A total of 216 healthy blood donors and 280 outpatients after solid organ transplantation were screened by a recombinant BoDV-1 ELISA followed by an indirect immunofluorescence assay (iIFA) as confirmatory test. For comparison, 288 serum and 258 cerebrospinal fluid (CSF) samples with a request for tick-borne encephalitis (TBE) diagnostics were analyzed for BoDV-1 infections. ELISA screening reactivity rates ranged from 3.5% to 18.6% depending on the cohort and the used ELISA antigen, but only one sample of a patient from the cohort with requested TBE diagnostics was confirmed to be positive for anti-BoDV-1-IgG by iIFA. In addition, the corresponding CSF sample of this patient with a three-week history of severe neurological disease tested positive for BoDV-1 RNA. Due to the iIFA results, all other results were interpreted as false-reactive in the ELISA screening. By linear serological epitope mapping, cross-reactions with human and bacterial proteins were identified as possible underlying mechanism for the false-reactive ELISA screening results. In conclusion, no oligo- or asymptomatic infections were detected in the studied cohorts. Serological tests based on a single recombinant BoDV-1 antigen should be interpreted with caution, and an iIFA should always be performed in addition.