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C-11 and F-18 Radiolabeling of Tetra- and Pentathiophenes as PET-Ligands for Amyloid Protein Aggregates
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Division of Molecular Imaging.
Linkoping Univ, Dept Chem, IFM, S-58183 Linkoping, Sweden..
Linkoping Univ, Dept Chem, IFM, S-58183 Linkoping, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform.
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2016 (English)In: ACS Medicinal Chemistry Letters, E-ISSN 1948-5875, Vol. 7, no 4, p. 368-373Article in journal (Refereed) Published
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Text
Abstract [en]

Three oligothiophenes were evaluated as PET ligands for the study of local and systemic amyloidosis ex vivo using tissue from patients with amyloid deposits and in vivo using healthy animals and PET-CT. The ex vivo binding studies revealed that all three labeled compounds bound specifically to human amyloid deposits. Specific binding was found in the heart, kidney, liver, and spleen. To verify the specificity of the oligothiophenes toward amyloid deposits, tissue sections with amyloid pathology were stained using the fluorescence exhibited by the compounds and evaluated with multiphoton microscopy. Furthermore, a in vivo monkey PET-CT study showed very low uptake in the brain, pancreas, and heart of the healthy animal indicating low nonspecific binding to healthy tissue. The biological evaluations indicated that this is a promising group of compounds for the visualization of systemic and localized amyloidosis.

Place, publisher, year, edition, pages
2016. Vol. 7, no 4, p. 368-373
Keywords [en]
Positron emission tomography, amyloidosis, amyloid-beta, transthyretin, AL amyloidosis, oligothiophenes
National Category
Pharmacology and Toxicology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
URN: urn:nbn:se:uu:diva-296858DOI: 10.1021/acsmedchemlett.5b00309ISI: 000374436700007PubMedID: 27096043OAI: oai:DiVA.org:uu-296858DiVA, id: diva2:940211
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research Göran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of TechnologyEU, European Research CouncilAvailable from: 2016-06-20 Created: 2016-06-20 Last updated: 2024-07-04Bibliographically approved

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Nordeman, PatrikEstrada, SergioWestermark, Gunilla T.Westermark, PerAntoni, Gunnar
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Division of Molecular ImagingPreclinical PET-MRI PlatformDepartment of Medical Cell BiologyClinical and experimental pathology
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