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

Acta Neuropathologica Communications, Journal Year: 2023, Volume and Issue: 11(1)

Published: Sept. 11, 2023

Abstract TSPO is a promising novel tracer target for positron-emission tomography (PET) imaging of brain tumors. However, due to the heterogeneity cell populations that contribute TSPO-PET signal, interpretation may be challenging. We therefore evaluated enrichment/expression in connection with its underlying histopathological and molecular features gliomas. analyzed expression regulatory mechanisms large silico datasets by performing direct bisulfite sequencing promotor. In glioblastoma tissue samples our study cohort, we dissected association enrichment protein labeling lineage markers immunohistochemistry fluorescence multiplex stains. Furthermore, identified relevant TSPO-associated signaling pathways RNA sequencing. found associated prognostically unfavorable glioma phenotypes promotor hypermethylation linked IDH mutation. Careful histological analysis revealed correlates signal expressed diverse populations. While tumor core areas are major contributor overall signals rim mainly driven CD68-positive microglia/macrophages. Molecularly, high marks subpopulations characterized an mesenchymal gene sets higher amounts tumor-associated macrophages. conclusion, improves understanding as marker gliomas unveiling IDH-dependent differences expression/regulation, regional PET functional implications terms immune interactions.

Language: Английский

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Multi-Targeted Neutron Capture Therapy Combined with an 18 kDa Translocator Protein-Targeted Boron Compound Is an Effective Strategy in a Rat Brain Tumor Model

Cancers, Journal Year: 2023, Volume and Issue: 15(4), P. 1034 - 1034

Published: Feb. 6, 2023

Boron neutron capture therapy (BNCT) has been adapted to high-grade gliomas (HG); however, some are refractory BNCT using boronophenylalanine (BPA). In this study, the feasibility of targeting 18 kDa translocator protein (TSPO) expressed in glioblastoma and surrounding environmental cells was investigated.Three rat glioma cell lines, an F98 bearing brain tumor model, DPA-BSTPG which is a boron-10 compound TSPO, BPA, sodium borocaptate (BSH) were used. TSPO expression evaluated model. uptake assessed three lines vitro vivo irradiation experiments performed.DPA-BSTPG efficiently taken up vitro. The 16-fold higher expressions than its tissue. biological effectiveness value 8.43 cells. boron concentration convection-enhanced delivery (CED) administration approximately twice as high BPA intravenous administration. significant efficacy over untreated group. combination gained significantly longer survival times alone.DPA-BSTPG with may provide multi-targeted against HG.

Language: Английский

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Machine learning-based approach reveals essential features for simplified TSPO PET quantification in ischemic stroke patients

Zeitschrift für Medizinische Physik, Journal Year: 2023, Volume and Issue: 34(2), P. 218 - 230

Published: Jan. 20, 2023

Neuroinflammation evaluation after acute ischemic stroke is a promising option for selecting an appropriate post-stroke treatment strategy. To assess neuroinflammation in vivo, translocator protein PET (TSPO PET) can be used. However, the gold standard TSPO quantification method includes 90 min scan and continuous arterial blood sampling, which challenging to perform on routine basis. In this work, we determine what information required simplified approach using machine learning algorithm. We analyzed data from 18 patients with who received 0–90 [18F]GE-180 as well T1-weigted (T1w), FLAIR, spin labeling (ASL) MRI scans. During scans, five manual venous samples at 5, 15, 30, 60, 85 post injection (p.i.) were drawn, plasma activity concentration was measured. Total distribution volume (VT) calculated Logan plot full dynamic image-derived input function (IDIF) carotid arteries. IDIF scaled by calibration factor derived all measured concentrations. The VT values used training random forest regressor. As features model, three late frames (60–70, 70–80, 80–90 p.i.), ASL image reflecting perfusion, voxel coordinates, lesion mask, algorithm validated leave-one-out approach. estimate impact of individual algorithm's performance, Shapley Additive Explanations (SHAP). Having determined that concentrations most important features, tested consisting dividing frame concentration. All combinations frames/samples compared means concordance correlation coefficient Bland-Altman plots. When predicted high accuracy (87.8 ± 8.3%) both non-lesion voxels. SHAP demonstrated p.i.) prediction, while influence ASL-derived mask low. Among concentrations, 70–80 p.i. divided 30 sample produced closest lesion. Reliable achievable single

Language: Английский

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18 kDa translocator protein positron emission tomography facilitates early and robust tumor detection in the immunocompetent SB28 glioblastoma mouse model

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: Oct. 17, 2022

Introduction The 18 kDa translocator protein (TSPO) receives growing interest as a biomarker in glioblastoma. Mouse models can serve an important tool for the investigation of biomarkers glioblastoma, but several glioblastoma indicated only low TSPO-PET signals contrast to high human Thus, we aimed investigate imaging syngeneic immunocompetent SB28 mouse model, which is thought closely represent tumor microenvironment (TME) Methods Dynamic TSPO-PET/CT was performed 60 min after injection 13.6 ± 4.2 MBq [ F]GE-180. Contrast enhanced CT (ceCT) acquired prior PET and served assessment volumes attenuation correction. sham mice were imaged at early (week-1; n = 6 SB28, sham) late time-point (week-3; 8 9 inoculation. Standard truth ex vivo obtained time-point. Tracer kinetics analyzed lesion site carotid arteries establish image derived input function (IDIF). ceCT compared with by calculation root-mean-square-errors (RMSE). Volumes distribution (VTmax/mean) calculated using IDIF standardized uptake values (SUVmax/mean) 40–60 time frame. Results Higher rate constants (K1) observed week-1 lesions when week-3 lesions. Highest agreement between achieved 50% maximum threshold (RMSE-VT: 39.7%; RMSE-SUV: 34.4%), similar (RMSE: 30.1%). Lesions had higher signal (VTmax 6.6 2.9 vs. 3.9 0.8, p 0.035; SUVmax 2.3 0.5 1.2 0.1, < 0.001) remained level 5.0 1.6 2.7 0.029; 1.9 0.2, 0.0012). VTmax correlated ( R 2 0.532, 0.001). Conclusion facilitates detection over tumors mirror could valuable translational model study TSPO biomarker.

Language: Английский

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

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 27, 2023

Abstract Various cellular sources hamper interpretation of positron-emission-tomography (PET) biomarkers in the tumor microenvironment (TME). We developed immunomagnetic cell sorting after vivo radiotracer injection (scRadiotracing) combination with 3D-histology via tissue clearing to dissect allocation PET signals TME. In SB28 glioblastoma mice, translocator protein (TSPO) uptake per was higher compared tumor-associated microglia/macrophages (TAMs). Cellular validated by proteomics and confirmed for vitro samples patients glioblastoma. Regional agreement between single tracer predicted individual distribution 3D-histology. consideration type abundance, cells were main contributor TSPO enrichment glioblastoma, however identified potential targets highly specific TAMs. Combining measures facilitates precise complex signal will serve validate novel TAM-specific radioligands.

Language: Английский

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[¹⁸F]SF51, a novel ¹⁸F-labeled PET radioligand for translocator protein 18kDa (TSPO) in brain, works well in monkeys but fails in humans

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 9, 2024

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Neurexin-3α-associated autoimmune encephalitis with intracranial diffuse large B lymphoma diagnosed on FDG and TSPO PET/MRI

European Journal of Nuclear Medicine and Molecular Imaging, Journal Year: 2022, Volume and Issue: 50(4), P. 1270 - 1272

Published: Dec. 6, 2022

Language: Английский

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