Multidentate (18)F-polypegylated styrylpyridines as imaging agents for Aβ plaques in cerebral amyloid angiopathy (CAA).
β-Amyloid plaques (Aβ plaques) in the brain are associated with cerebral amyloid angiopathy (CAA). Imaging agents that could target the Aβ plaques in the living human brain would be potentially valuable as biomarkers in patients with CAA. A new series of (18)F styrylpyridine derivatives with high molecular weights for selectively targeting Aβ plaques in the blood vessels of the brain but excluded from the brain parenchyma is reported. The styrylpyridine derivatives, 8a-c, display high binding affinities and specificity to Aβ plaques (K(i) = 2.87, 3.24, and 7.71 nM, respectively). In vitro autoradiography of [(18)F]8a shows labeling of β-amyloid plaques associated with blood vessel walls in human brain sections of subjects with CAA and also in the tissue of AD brain sections. The results suggest that [(18)F]8a may be a useful PET imaging agent for selectively detecting Aβ plaques associated with cerebral vessels in the living human brain.
Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Zhihao
Z
Zha
Seok Rye
SR
Choi
Karl
K
Ploessl
Brian P
BP
Lieberman
Wenchao
W
Qu
Franz
F
Hefti
Mark
M
Mintun
Daniel
D
Skovronsky
Hank F
HF
Kung
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000098:blood supply; D016657:Cerebral Amyloid Angiopathy / Q000000981:diagnostic imaging* / Q000473:pathology; D005462:Fluorine Radioisotopes; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000473:pathology; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution
C570405:2-(2-fluoroethoxy)-1,3-di(2-(2-(2-(5-(4-(methylamino)styryl)pyridin-2-yloxy)ethoxy)ethoxy)ethoxy)propane; D016229:Amyloid beta-Peptides; D005462:Fluorine Radioisotopes; D011725:Pyridines; D019275:Radiopharmaceuticals; D013343:Styrenes