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C-11 and F-18 Radiolabeling of Tetra- and Pentathiophenes as PET-Ligands for Amyloid Protein Aggregates
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för Molekylär Avbildning.
Linkoping Univ, Dept Chem, IFM, S-58183 Linkoping, Sweden..
Linkoping Univ, Dept Chem, IFM, S-58183 Linkoping, Sweden..
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för Preklinisk PET-MRI.
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2016 (engelsk)Inngår i: ACS Medicinal Chemistry Letters, ISSN 1948-5875, E-ISSN 1948-5875, Vol. 7, nr 4, s. 368-373Artikkel i tidsskrift (Fagfellevurdert) Published
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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.

sted, utgiver, år, opplag, sider
2016. Vol. 7, nr 4, s. 368-373
Emneord [en]
Positron emission tomography, amyloidosis, amyloid-beta, transthyretin, AL amyloidosis, oligothiophenes
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Patologi
Identifikatorer
URN: urn:nbn:se:uu:diva-296858DOI: 10.1021/acsmedchemlett.5b00309ISI: 000374436700007PubMedID: 27096043OAI: oai:DiVA.org:uu-296858DiVA, id: diva2:940211
Forskningsfinansiär
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 CouncilTilgjengelig fra: 2016-06-20 Laget: 2016-06-20 Sist oppdatert: 2019-03-29bibliografisk kontrollert

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