Biomedicines, Год журнала: 2024, Номер 12(1), С. 188 - 188
Опубликована: Янв. 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
Язык: Английский
Cell, Год журнала: 2023, Номер 186(17), С. 3706 - 3725.e29
Опубликована: Авг. 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.
Язык: Английский
Процитировано
70
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Май 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.
Язык: Английский
Процитировано
3
Genomic psychiatry :, Год журнала: 2025, Номер unknown, С. 1 - 6
Опубликована: Апрель 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.
Язык: Английский
Процитировано
0
Acta Neuropathologica, Год журнала: 2024, Номер 148(1)
Опубликована: Ноя. 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.
Язык: Английский
Процитировано
2
NeuroImage, Год журнала: 2024, Номер 300, С. 120860 - 120860
Опубликована: Сен. 25, 2024
Язык: Английский
Процитировано
1
Theranostics, Год журнала: 2024, Номер 14(16), С. 6319 - 6336
Опубликована: Янв. 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
Язык: Английский
Процитировано
1
Neuro-Oncology Advances, Год журнала: 2024, Номер 6(1)
Опубликована: Янв. 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.
Язык: Английский
Процитировано
1
medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Апрель 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.
Язык: Английский
Процитировано
0
Clinical Cancer Research, Год журнала: 2024, Номер 30(20), С. 4618 - 4634
Опубликована: Авг. 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.
Язык: Английский
Процитировано
0
Molecular Neurodegeneration, Год журнала: 2024, Номер 19(1)
Опубликована: Сен. 5, 2024
Язык: Английский
Процитировано
0