Differential Spatial Distribution of TSPO or Amino Acid PET Signal and MRI Contrast Enhancement in Gliomas

Cancers, Journal Year: 2021, Volume and Issue: 14(1), P. 53 - 53

Published: Dec. 23, 2021

In this study, dual PET and contrast enhanced MRI were combined to investigate their correlation per voxel in patients at initial diagnosis with suspected glioblastoma. Correlation enhancement (CE) as an indicator of BBB leakage was further used evaluate whether signal is likely caused by disruption alone, or rather attributable specific binding after passage. images [18F]GE180 the amino acid [18F]FET acquired normalized healthy background (tumor-to-background ratio, TBR). Contrast pre-contrast T1-weighted generate relative CE values (rCE). Voxel-wise analysis revealed a high even within sub-volumes without detectable CE. No moderate rCE TBR voxel-values small overlap well larger distance hotspots delineated TBR-PET detected. contrast, voxel-wise between both modalities strong for most showed distance. The tumor observed discordant emphasize specificity signals relevance differential information from images.

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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Multi-tracer and multiparametric PET imaging to detect the IDH mutation in glioma: a preclinical translational in vitro, in vivo, and ex vivo study

Cancer Imaging, Journal Year: 2022, Volume and Issue: 22(1)

Published: March 18, 2022

This translational study explores multi-tracer PET imaging for the non-invasive detection of IDH1 mutation which is a positive prognostic factor in glioma.U87 human high-grade glioma (HGG) isogenic cell lines with or without (CRISP/Cas9 method) were stereotactically grafted into rat brains, and examined, vitro, vivo ex vivo. sessions, radiotracers specific glycolytic metabolism ([18F]FDG), amino acid ([18F]FDopa), inflammation ([18F]DPA-714), performed sequentially during 3-4 days. The vitro radiotracer uptake was expressed as percent per million cells. For each examined vivo, static analyses included maximal mean tumor-to-background ratio (TBRmax TBRmean) metabolic tumor volume (MTV). Dynamic distribution (DVR) relative residence time (RRT) extracted from reference Logan model. Ex consisted immunological analyses.In IDH1+ cells (i.e. expressing mutation) showed lower levels [18F]DPA-714 compared to IDH1- (p < 0.01). These results confirmed IDH+ tumors (3.90 versus 5.52 TBRmax, p = 0.03). Different values [18F] FDopa RRT (respectively 11.07 22.33 2.69 - 1.81 IDH- tumors, 0.02) also observed between two types tumors. provided best diagnostic performance discriminate (AUC 100%, Immuno-histological revealed expression Iba-1 TSPO antibodies tumors.[18F]DPA-714 both correlate presence HGG. are therefore good candidates studies investigating their clinical applications patients.

Language: Английский

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Longitudinal [18F]GE-180 PET Imaging Facilitates In Vivo Monitoring of TSPO Expression in the GL261 Glioblastoma Mouse Model

Biomedicines, Journal Year: 2022, Volume and Issue: 10(4), P. 738 - 738

Published: March 22, 2022

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

Language: Английский

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[¹⁸F]BIBD-239: ¹⁸F-Labeled ER176, a Positron Emission Tomography Tracer Specific for the Translocator Protein

Molecular Pharmaceutics, Journal Year: 2022, Volume and Issue: 19(7), P. 2351 - 2366

Published: June 7, 2022

[11C]ER176 has adequate sensitivity to image the human brain translocator protein (TSPO) in all three genotypes by positron emission tomography (PET). However, its clinical application is limited short half-life of 11C (20.38 min). To overcome deficiency and keep pharmacophore features ER176 maximum extent, we designed four fluorine-labeled derivatives using deuterium method. In vitro competition binding confirmed that compounds had high affinity for TSPO. Biodistribution experiments showed tissues with expression TSPO uptake these compounds, as well compound penetration mild defluorination vivo. Therefore, [18F]BIBD-239 simple synthesis conditions was selected further biological evaluation. Theoretical simulations BIBD-239 have similar modes sites Ala147-TSPO Thr147-TSPO, which indicated tracers may consistent genotypes. autoradiography vivo PET studies ischemic rat dramatically higher on lesion site compared contralateral side good kinetics. Additionally, provided clear tumor images a GL261 glioma model. Importantly, imaging liquid chromatography–high-resolution mass spectrometry (LC-HRMS) results other metabolites did not interfere imaging. Conclusively, [18F]BIBD-239, low polymorphism sensitivity, labeling conditions, yield, affinity, specificity TSPO, it planned evaluation species.

Language: Английский

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Imaging Metformin Efficacy as Add-On Therapy in Cells and Mouse Models of Human EGFR Glioblastoma

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: May 3, 2021

Glioblastoma (GBM) is a highly aggressive tumor of the brain. Despite efforts, response to current therapies poor and 2-years survival rate ranging from 6-12%. Here, we evaluated preclinical efficacy Metformin (MET) as add-on therapy Temozolomide (TMZ) ability [ 18 F]FLT (activity thymidine kinase 1 related cell proliferation) F]VC701 (translocator protein, TSPO) Positron Emission Tomography (PET) radiotracers predict therapy. Indeed, TSPO expressed on outer mitochondrial membrane activated microglia/macrophages, cells, astrocytes endothelial cells. TMZ-sensitive (Gli36ΔEGFR-1 L0627) or -resistant (Gli36ΔEGFR-2) GBM lines representative classical molecular subtype were tested in vitro vivo orthotopic mouse models. Our results indicate that , MET increased TMZ TMZ-resistant cells by deregulating balance between pro-survival ( bcl2 ) pro-apoptotic bax/bad Bcl-family members promoting early apoptosis both Gli36ΔEGFR-1 Gli36ΔEGFR-2 In significantly extended median tumor-bearing mice compared TMZ-treated ones reduced recurrence PET studies with proliferation radiopharmaceutical performed at time during treatment able distinguish responder non-responder but not duration effect. On contrary, uptake was only treated plus levels negatively correlated animals’ survival. Overall, our data showed addition improved models increasing reducing relapsing rate. Finally, imaging suggest reduction represents common mechanism combined treatment, whereas last reduce TSPO. This associated response. TSPO-ligand may be used complementary marker microenvironment effects.

Language: Английский

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Hybrid PET/MRI in Neuro-oncology: Current Status and Perspectives

Published: June 1, 2023

Advanced MRI methods and PET using radiolabeled amino acids provide valuable information in addition to conventional MR imaging for brain tumor diagnostics. These are particularly helpful challenging situations such as the differentiation of malignant processes from benign lesions, identification non-enhancing glioma subregions, progression treatment-related changes, early assessment response anticancer therapy. The debate over which is preferable situation ongoing has been addressed numerous studies. Currently, most radiology nuclear medicine departments perform these examinations independently each other leading multiple patient. advent hybrid PET/MRI allowed a convergence but date simultaneous reached little relevance clinical neuro-oncology. This partly due limited availability scanners, also fact that second-line examination tumors. only required equivocal situations, spatial co-registration previous possible without disadvantage. A key factor benefit neuro-oncology multimodal approach provides decisive improvements diagnostics tumors compared with single modality. systematic review focuses on studies were able demonstrate additive value acid ‘advanced’ diagnosis Available suggest combination advanced improves grading histomolecular characterization newly diagnosed However, data concerning delineation extent biopsy guidance value. clear diagnostic can be achieved regarding recurrence changes. Here, PET-guided evaluation seems helpful. In summary, there growing evidence achieve tumors, offers optimal conditions.

Language: Английский

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MRI and PET of Brain Tumor Neuroinflammation in the Era of Immunotherapy, From the AJR Special Series on Inflammation

American Journal of Roentgenology, Journal Year: 2021, Volume and Issue: 218(4), P. 582 - 596

Published: July 14, 2021

With the emergence of immune-modulating therapies, brain tumors present important diagnostic imaging challenges. These challenges include planning personalized treatment and adjudicating accurate monitoring approaches therapeutically specific response criteria. The have been due, in part reliance on nonspecific metrics, such as gadolinium contrast-enhanced MRI or FDG PET, rapidly evolving biologic understanding neuroinflammation. importance tumor immune interaction ability to augment inflammation improve clinical outcomes make it necessary for radiologists develop a working knowledge system its role neuroimaging. purpose this article is review relevant concepts microenvironment primary metastatic tumors, interactions between system, PET methods inflammatory elements associated with these malignancies. In recognition growing fields immunotherapeutics precision oncology, clinically translatable metrics diagnosis neuroinflammation are highlighted. Practical guidance provided implementing iron nanoparticle imaging, including indications, protocols, interpretation, pitfalls. A comprehensive mechanisms within their features will facilitate development innovative noninvasive prognostic predictive strategies oncology.

Language: Английский

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Increased TSPO PET signal after radiochemotherapy in IDH-wildtype glioma—indicator for treatment-induced immune activation?

European Journal of Nuclear Medicine and Molecular Imaging, Journal Year: 2022, Volume and Issue: 49(12), P. 4282 - 4283

Published: May 25, 2022

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, &lt; 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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