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

Deciphering sources of PET signals in the tumor microenvironment of glioblastoma at cellular resolution DOI Creative Commons
Laura M. Bartos, Sabrina V. Kirchleitner, Zeynep Ilgin Kolabas

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(43)

Published: Oct. 27, 2023

Various cellular sources hamper interpretation of positron emission tomography (PET) biomarkers in the tumor microenvironment (TME). We developed an approach immunomagnetic cell sorting after vivo radiotracer injection (scRadiotracing) with three-dimensional (3D) histology to dissect allocation PET signals TME. In mice implanted glioblastoma, translocator protein (TSPO) uptake per was higher compared tumor-associated microglia/macrophages (TAMs), validated by levels. Translation vitro scRadiotracing patients glioma immediately resection confirmed single-cell TSPO tracer cells immune cells. Across species, explained heterogeneity individual TSPO-PET signals. consideration and type abundance, were main contributor enrichment glioblastoma; however, proteomics identified potential targets highly specific for TAMs. Combining measures 3D facilitates precise serves validate emerging novel TAM-specific radioligands.

Language: Английский

Citations

10
Towards multicenter β-amyloid PET imaging in mouse models: A triple scanner head-to-head comparison DOI Creative Commons
Johannes Gnörich,

Mara Koehler,

Karin Wind

et al.

NeuroImage, Journal Year: 2024, Volume and Issue: 297, P. 120748 - 120748

Published: July 26, 2024

β-amyloid (Aβ) small animal PET facilitates quantification of fibrillar amyloidosis in Alzheimer's disease (AD) mouse models. Thus, the methodology is receiving growing interest as a monitoring tool preclinical drug trials. In this regard, harmonization data from different scanners at multiple sites would allow establishment large collaborative cohorts and may facilitate efficacy comparison treatments. Therefore, we objected to determine level agreement Aβ-PET by head-to-head three state-of-the-art scanners, which could help pave way for future multicenter studies.

Language: Английский

Citations

2
Microglial Imaging in Alzheimer’s Disease and Its Relationship to Brain Amyloid: A Human 18F-GE180 PET Study DOI
Zhengshi Yang, Sarah J. Banks,

Aaron Ritter

et al.

Journal of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: 96(4), P. 1505 - 1514

Published: Nov. 17, 2023

Background:Emerging evidence suggests a potential causal role of neuroinflammation in Alzheimer's disease (AD). Using positron emission tomography (PET) to image overexpressed 18 kDA translocator protein (TSPO) by activated microglia has gained increasing interest. The uptake 18F-GE180 TSPO PET was observed co-localize with inflammatory markers and have two-stage association amyloid mice. Very few studies evaluated the diagnostic power AD population its interpretation human remains controversial about whether it is marker microglial activation or merely reflects disrupted blood-brain barrier integrity humans. Objective:The goal this study GE180 from perspective previous animal observations. Methods:With data twenty-four participants having 18F-AV45 scans, we group differences between without cognitive impairment. An analysis then conducted test if relationship humans consistent mouse model. Results:Elevated impairment compared those normal cognition. No regions showed reduced uptake. Consistent model, observed. Conclusions:18F-GE180 imaging promising utility detecting pathological alterations symptomatic population. suggested that might be considerably influenced activation.

Language: Английский

Citations

3
A feasibility study for quantitative assessment of cerebrovascular malformations using flutriciclamide ([18F]GE-180) PET/MRI DOI Creative Commons

Sally Ji Who Kim,

Janine M. Lupo, Yicheng Chen

et al.

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: April 5, 2023

Neuroinflammation plays a key role in both the pathogenesis and progression of cerebral cavernous malformations (CCM). Flutriciclamide ([18F]GE-180) is translocator protein (TSPO) targeting positron emission tomography (PET) tracer, developed for imaging neuroinflammation. The objectives this study were to describe characteristics flutriciclamide uptake different brain tissue regions CCM patients compared controls, evaluate iron deposition within lesions.Five with six controls underwent 60 or 90 min continuous PET/MRI scan following 315 ± 68.9 MBq administration. Standardized value (SUV) standardized ratio (SUVr) obtained using striatum as pseudo-reference. Quantitative susceptibility maps (QSM) used define location vascular malformation calculate amount each lesion.Increased was observed all lesions. temporal pole demonstrated highest radiotracer uptake; paracentral lobule, cuneus hippocampus exhibited moderate while had lowest uptake, average SUVs 0.66, 0.55, 0.63, 0.33 patient 0.57, 0.50, 0.48, 0.42, 0.32 respectively. Regional SUVr showed similar trends. SUV QSM values lesions 0.58 0.23 g/ml 0.30 0.10 ppm. positively correlated (r = 0.53, p 0.03).The distribution human potential TSPO PET tracer marker neuroinflammation that may be relevant characterizing disease along QSM.

Language: Английский

Citations

2
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
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

Citations

0
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