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ACS Med Chem Lett. 2016 Feb 18;7(4):368-73. doi: 10.1021/acsmedchemlett.5b00309. eCollection 2016 Apr 14.

(11)C and (18)F Radiolabeling of Tetra- and Pentathiophenes as PET-Ligands for Amyloid Protein Aggregates.

Author information

1
Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University , Uppsala SE-75123, Sweden.
2
Department of Chemistry, IFM, Linköping University , Linköping 581 83, Sweden.
3
Department of Medicinal Cell Biology, Uppsala University , Uppsala SE-75123, Sweden.
4
Department of Immunology, Genetics and Pathology, Uppsala University , Uppsala SE-75123, Sweden.
5
Department of Pharmacology, University of Oslo , Oslo 0316, Norway.

Abstract

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.

KEYWORDS:

AL amyloidosis; Positron emission tomography; amyloid-β; amyloidosis; oligothiophenes; transthyretin

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