Non-invasive imaging of tau-targeted probe uptake by whole brain multi-spectral optoacoustic tomography.
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 no...
| Publicado en: | European Journal of Nuclear Medicine & Molecular Imaging Vol. 49; no. 7; pp. 2137 - 2153 |
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| Autores principales: | , , , , , , , , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Jun2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=157024682&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 157024682 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 16197070 NPC jtl: European Journal of Nuclear Medicine & Molecular Imaging issn: 16197070 maglogo: N pubinfo: dt: Jun2022 vid: 49 iid: 7 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 157024682 155085857 10.1007/s00259-022-05708-w 157024682 ppf: 2137 ppct: 16 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Non-invasive imaging of tau-targeted probe uptake by whole brain multi-spectral optoacoustic tomography. aug: au: Vagenknecht, Patrick Luzgin, Artur Ono, Maiko Ji, Bin Higuchi, Makoto Noain, Daniela Maschio, Cinzia A. Sobek, Jens Chen, Zhenyue Konietzko, Uwe Gerez, Juan A. Riek, Roland Razansky, Daniel Klohs, Jan Nitsch, Roger M. Dean-Ben, Xose Luis Ni, Ruiqing affil: Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland sug: ab: 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. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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