Back to Search
Start Over
Non-invasive imaging of tau-targeted probe uptake by whole brain multi-spectral optoacoustic tomography
- Source :
- European Journal of Nuclear Medicine and Molecular Imaging, 49 (7)
- Publication Year :
- 2022
-
Abstract
- Purpose Abnormal tau accumulation within the brain plays an important role in tauopathies such as Alzheimer’s disease and frontotemporal dementia. High-resolution imaging of tau deposits at the whole-brain scale in animal disease models is highly desired. Methods We approached this challenge by non-invasively imaging the brains of P301L mice of 4-repeat tau with concurrent volumetric multi-spectral optoacoustic tomography (vMSOT) at ~ 115 μm spatial resolution using the tau-targeted pyridinyl-butadienyl-benzothiazole derivative PBB5 (i.v.). In vitro probe characterization, concurrent vMSOT and epi-fluorescence imaging of in vivo PBB5 targeting (i.v.) was performed in P301L and wild-type mice, followed by ex vivo validation using AT-8 antibody for phosphorylated tau. Results PBB5 showed specific binding to recombinant K18 tau fibrils by fluorescence assay, to post-mortem Alzheimer’s disease brain tissue homogenate by competitive binding against [11C]PBB3 and to tau deposits (AT-8 positive) in post-mortem corticobasal degeneration and progressive supranuclear palsy brains. Dose-dependent optoacoustic and fluorescence signal intensities were observed in the mouse brains following i.v. administration of different concentrations of PBB5. In vivo vMSOT brain imaging of P301L mice showed higher retention of PBB5 in the tau-laden cortex and hippocampus compared to wild-type mice, as confirmed by ex vivo vMSOT, epi-fluorescence, multiphoton microscopy, and immunofluorescence staining. Conclusions We demonstrated non-invasive whole-brain imaging of tau in P301L mice with vMSOT system using PBB5 at a previously unachieved ~ 115 μm spatial resolution. This platform provides a new tool to study tau spreading and clearance in a tauopathy mouse model, foreseeable in monitoring tau targeting putative therapeutics.<br />European Journal of Nuclear Medicine and Molecular Imaging, 49 (7)<br />ISSN:1619-7070<br />ISSN:1619-7089
- Subjects :
- Pathology
medicine.medical_specialty
Animal model
Fluorescence imaging
Frontotemporal dementia
Optoacoustic imaging
Tau
Mice, Transgenic
tau Proteins
610 Medicine & health
Progressive supranuclear palsy
170 Ethics
Mice
chemistry.chemical_compound
Neuroimaging
Alzheimer Disease
In vivo
medicine
Animals
Humans
Corticobasal degeneration
2741 Radiology, Nuclear Medicine and Imaging
Radiology, Nuclear Medicine and imaging
10237 Institute of Biomedical Engineering
Brain
General Medicine
Human brain
11359 Institute for Regenerative Medicine (IREM)
medicine.disease
Disease Models, Animal
medicine.anatomical_structure
Tauopathies
chemistry
Positron-Emission Tomography
Thioflavin
Tauopathy
Alzheimer's disease
Subjects
Details
- Language :
- English
- ISSN :
- 16197070 and 16197089
- Database :
- OpenAIRE
- Journal :
- European Journal of Nuclear Medicine and Molecular Imaging, 49 (7)
- Accession number :
- edsair.doi.dedup.....df56bed12dcaf421dbb88fe0835e4200