The Traumatic Inoculation Process Affects TSPO Radioligand Uptake in Experimental Orthotopic Glioblastoma DOI Creative Commons

Lukas Gold,

Enio Barci, Matthias Brendel

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(1), P. 188 - 188

Published: Jan. 15, 2024

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 various sources TSPO PET signal. This work investigates impact inoculation-driven immune response on signal in experimental orthotopic

Language: Английский

Distinct molecular profiles of skull bone marrow in health and neurological disorders DOI Creative Commons
Zeynep Ilgin Kolabas,

Louis B. Kuemmerle,

Robert Perneczky

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(17), P. 3706 - 3725.e29

Published: Aug. 1, 2023

The bone marrow in the skull is important for shaping immune responses brain and meninges, but its molecular makeup among bones relevance human diseases remain unclear. Here, we show that mouse has most distinct transcriptomic profile compared with other states of health injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals distinct, differentially expressed neutrophil-related pathways unique synaptic protein signature. 3D imaging demonstrates structural cellular details skull-meninges connections (SMCs) veins. Last, using translocator positron emission tomography (TSPO-PET) imaging, reflects inflammatory disease-specific spatial distribution patients various neurological disorders. anatomical functional potential as site diagnosing, monitoring, treating diseases.

Language: Английский

Citations

70

Neuronal and oligodendroglial but not astroglial tau translates to in vivo tau-PET signals in primary tauopathies DOI Creative Commons

Luna Slemann,

Johannes Gnörich,

Selina Hummel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 7, 2024

Summary Tau-PET receives growing interest as an imaging biomarker for the 4-repeat tauopathy progressive supranuclear palsy (PSP). However, translation of in vitro 4R-tau binding to vivo tau-PET signals is still unclear. Therefore, we conducted a longitudinal [ 18 F]PI-2620 PET/MRI study 4-repeat-tau mouse model (PS19) and found elevated PET signal presence high neuronal tau. Cell sorting after radiotracer injection revealed higher tracer uptake single neurons compared astrocytes PS19 mice. Regional during lifetime correlated with abundance fibrillary tau subsequent autopsy samples PSP patients disease controls. In autoradiography, tau-positive oligodendrocytes AT8 density but not were driver autoradiography PSP. summary, oligodendroglial constitutes dominant source 4-repeat-tauopathies, yielding capacity translate signal.

Language: Английский

Citations

3

Illuminating synucleinopathies: Advances in α-synuclein PET tracer development for in vivo neuroimaging DOI
Yingfang He,

Lan Qin,

Qing Ye

et al.

Genomic psychiatry :, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 6

Published: April 29, 2025

Abnormal α-synuclein aggregation is a pathological hallmark of Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies. A suitable radiotracer that can noninvasively map synucleinopathies through positron emission tomography (PET) will lead to breakthroughs in early diagnosis, monitoring disease progression, evaluating treatment responses. However, the development PET tracers for lagging due several challenges. In this perspective, we provide brief review advancements targeting summarize recent clinical studies aimed at mapping neurodegenerative patients using these tracers.

Language: Английский

Citations

0

Neuronal and oligodendroglial, but not astroglial, tau translates to in vivo tau PET signals in individuals with primary tauopathies DOI Creative Commons

Luna Slemann,

Johannes Gnörich, Selina Hummel

et al.

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 148(1)

Published: Nov. 24, 2024

Abstract Tau PET has attracted increasing interest as an imaging biomarker for 4-repeat (4R)-tauopathy progressive supranuclear palsy (PSP). However, the translation of in vitro 4R-tau binding to vivo tau signals is still unclear. Therefore, we performed a translational study using broad spectrum advanced methodologies investigate sources [ 18 F]PI-2620 individuals with 4R-tauopathies, including pilot autopsy patients. First, conducted longitudinal PET/MRI 4-repeat-tau mouse model (PS19) and detected elevated presence high levels neuronal tau. An innovative approach involving cell sorting after radiotracer injection revealed higher tracer uptake single neurons than astrocytes PS19 mice. Regional during lifetime correlated abundance fibrillary autoradiography signal intensity PSP patients disease controls who underwent 2–63 months PET. In autoradiography, tau-positive oligodendrocytes AT8 density, but not astrocytes, were drivers PSP. The at boundary gray white matter facilitated identification optimized frontal lobe target region detect burden summary, oligodendroglial constitutes dominant source 4-repeat-tauopathies, translating signal.

Language: Английский

Citations

2

Astroglial glucose uptake determines brain FDG-PET alterations and metabolic connectivity during healthy aging in mice DOI Creative Commons
Laura M. Bartos,

Sebastian T. Kunte,

Stephan Wagner

et al.

NeuroImage, Journal Year: 2024, Volume and Issue: 300, P. 120860 - 120860

Published: Sept. 25, 2024

Language: Английский

Citations

1

PET imaging of microglia in Alzheimer's disease using copper-64 labeled TREM2 antibodies DOI Creative Commons

Monireh Shojaei,

Rebecca Schaefer, Kai Schlepckow

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(16), P. 6319 - 6336

Published: Jan. 1, 2024

Triggering receptor expressed on myeloid cells 2 (TREM2) plays an essential role in microglia activation and is being investigated as a potential therapeutic target for modulation of several neurological diseases. In this study, we present the development preclinical evaluation

Language: Английский

Citations

1

Evidence for inflammation in normal appearing brain regions in patients with growing sporadic vestibular schwannoma: a PET study DOI Creative Commons
Bandar Alfaifi, Rainer Hinz, Alan Jackson

et al.

Neuro-Oncology Advances, Journal Year: 2024, Volume and Issue: 6(1)

Published: Jan. 1, 2024

Abstract Background Nonauditory symptoms can be a prominent feature in patients with sporadic vestibular schwannoma (VS), but the cause of these is unknown. Inflammation hypothesized to play key role growth and symptomatic presentation VS, this study, we investigated through translocator protein (TSPO) positron emission tomography (PET) whether inflammation occurred within “normal appearing” brain such its association tumor growth. Methods Dynamic PET datasets from 15 VS (8 static 7 growing) who had been previously imaged using TSPO tracer [11C](R)-PK11195 were included. Parametric images binding potential (BPND) distribution volume ratio (DVR) derived compared across groups both contralateral ipsilateral gray (GM) white matter (WM) regions. Voxel-wise cluster analysis was additionally performed identify anatomical regions increased binding. Results Compared tumors, growing demonstrated significantly higher cortical (GM, 1.070 vs. 1.031, P = .03) whole (GM & WM, 1.045 1.006, DVR values. The voxel-wise supported region-based revealed clusters high precentral, postcentral, prefrontal cortex VS. Conclusions We present first vivo evidence expression brains These results provide mechanistic insight into development nonauditory highlight need for further studies interrogating neuroinflammation driving symptomatology.

Language: Английский

Citations

1

Remote Neuroinflammation in Newly Diagnosed Glioblastoma Correlates with Unfavorable Clinical Outcome DOI
Laura M. Bartos, Stefanie Quach,

Valerio Zenatti

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 24, 2024

Abstract Local therapy strategies still provide only limited success in the treatment of glioblastoma, most frequent primary brain tumor adults, indicating global involvement this fatal disease. To study impact neuroinflammation distant site on clinical course patients with we performed translocator protein (TSPO)-PET newly diagnosed glioma WHO 2 and healthy controls compared signals non-lesion (i.e. contralateral) hemisphere. Back-translation syngeneic glioblastoma mice was used to characterize PET alterations a cellular level. Ultimately, multiplex gene expression analyses served profile immune cells remote brain. Our revealed elevated TSPO-PET contralateral hemispheres controls. Contralateral TSPO associated persisting epilepsy short survival independent phenotype. pinpointed myeloid as source signal increases complex signature comprised joint cell activation immunosuppression regions. In brief, within hemisphere is poor outcome glioblastoma. serves detect who may benefit from immunomodulatory strategies.

Language: Английский

Citations

0

Remote Neuroinflammation in Newly Diagnosed Glioblastoma Correlates with Unfavorable Clinical Outcome DOI Creative Commons
Laura M. Bartos, Stefanie Quach,

Valerio Zenatti

et al.

Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 30(20), P. 4618 - 4634

Published: Aug. 16, 2024

Current therapy strategies still provide only limited success in the treatment of glioblastoma, most frequent primary brain tumor adults. In addition to characterization microenvironment, global changes patients with glioblastoma have been described. However, impact and molecular signature neuroinflammation distant site not yet thoroughly elucidated.

Language: Английский

Citations

0

Regional desynchronization of microglial activity is associated with cognitive decline in Alzheimer’s disease DOI Creative Commons
Artem Zatcepin, Johannes Gnörich, Boris‐Stephan Rauchmann

et al.

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: Sept. 5, 2024

Language: Английский

Citations

0