11C and 18FRadiolabeling of Tetra- and Pentathiophenes as PET-ligands for Amyloid Protein Aggregates
2016 (English)In: ACS Medicinal Chemistry Letters, ISSN 1948-5875, E-ISSN 1948-5875, Vol. 7, no 4, 368-373 p.Article in journal (Refereed) Published
Three oligothiophenes were evaluated as PET tracers 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 towards amyloid deposits, tissue sections with amyloid pathology were stained using the fluorescence exhibited by the compounds and evaluated with multiphoton microscopy. Furthermore, in vivo rat and monkey PET-CT studies showed very low uptake in the brain, pancreas and heart of the healthy animals indicating low non-specific 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
American Chemical Society (ACS), 2016. Vol. 7, no 4, 368-373 p.
Chemical Sciences Cell Biology
IdentifiersURN: urn:nbn:se:liu:diva-122273DOI: 10.1021/acsmedchemlett.5b00309ISI: 000374436700007OAI: oai:DiVA.org:liu-122273DiVA: diva2:865139
Funding agencies: Swedish Research Council; Swedish Foundation for Strategic Research; LiU-Neuro; Ehrling-Persson Foundation; Goran-Gustafsson Foundation; ERC Starting Independent Researcher grant (Project: MUMID)
Vid tiden för disputation förelåg publikationen som manuskript2015-10-272015-10-272016-05-12Bibliographically approved