(11)C and (18)F Radiolabeling of Tetra- and Pentathiophenes as PET-Ligands for Amyloid Protein Aggregates.
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.
Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University , Uppsala SE-75123, Sweden.
Patrik
P
Nordeman
Department of Chemistry, IFM, Linköping University , Linköping 581 83, Sweden.
Leif B G
LB
Johansson
Department of Chemistry, IFM, Linköping University , Linköping 581 83, Sweden.
Marcus
M
Bäck
Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University , Uppsala SE-75123, Sweden.
Sergio
S
Estrada
Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University , Uppsala SE-75123, Sweden.
Håkan
H
Hall
Department of Chemistry, IFM, Linköping University , Linköping 581 83, Sweden.
Daniel
D
Sjölander
Department of Medicinal Cell Biology, Uppsala University , Uppsala SE-75123, Sweden.
Gunilla T
GT
Westermark
Department of Immunology, Genetics and Pathology, Uppsala University , Uppsala SE-75123, Sweden.
Per
P
Westermark
Department of Pharmacology, University of Oslo , Oslo 0316, Norway.
Lars
L
Nilsson
Department of Chemistry, IFM, Linköping University , Linköping 581 83, Sweden.
Per
P
Hammarström
Department of Chemistry, IFM, Linköping University , Linköping 581 83, Sweden.
K Peter R
KP
Nilsson
Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University , Uppsala SE-75123, Sweden.
Gunnar
G
Antoni
AL amyloidosis; Positron emission tomography; amyloid-β; amyloidosis; oligothiophenes; transthyretin