Abstract
In the present study, a styryltriazole and four resveratrol derivatives were synthesized as candidates for β-amyloid (Aβ) plaque imaging. On the basis of their binding affinities to Aβ(1-42) aggregates, the styryltriazole (1, K(i) = 12.8 nM) and one resveratrol derivative (5, K(i) = 0.49 nM) were labeled with (18)F. In normal mice, tissue distribution of [(18)F]5 showed good initial brain uptake (3.26% ID/g at 2 min) but slow wash-out from brains (2-to-60 min uptake ratio: 2.9). Furthermore, it underwent in vivo metabolic defluorination (1.88% ID/g at 2 min and 9.73% ID/g at 60 min). In contrast, [(18)F]1 displayed high initial brain uptake (5.38% ID/g at 2 min) with rapid wash-out from brains (0.52% ID/g at 60 min; 2-to-60 min uptake ratio: 10.3). These results indicate that [(18)F]1 has in vivo kinetics comparable to PET radiopharmaceuticals currently under commercial development, demonstrating that [(18)F]1 is a desirable PET radioligand for Aβ plaque imaging.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyloid beta-Peptides / metabolism*
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Aniline Compounds / chemical synthesis*
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Aniline Compounds / chemistry
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Aniline Compounds / pharmacokinetics
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Animals
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Brain / diagnostic imaging
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Brain / metabolism*
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Fluorine Radioisotopes
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Male
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Mice
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Mice, Inbred ICR
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Peptide Fragments / metabolism
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Plaque, Amyloid / metabolism*
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Radioligand Assay
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Radionuclide Imaging
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Radiopharmaceuticals / chemical synthesis*
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Radiopharmaceuticals / chemistry
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Radiopharmaceuticals / pharmacokinetics
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Resveratrol
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Stereoisomerism
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Stilbenes / chemical synthesis*
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Stilbenes / chemistry
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Stilbenes / pharmacokinetics
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Structure-Activity Relationship
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Styrenes / chemical synthesis*
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Styrenes / chemistry
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Styrenes / pharmacokinetics
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Tissue Distribution
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Triazoles / chemical synthesis*
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Triazoles / chemistry
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Triazoles / pharmacokinetics
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Triazoles / pharmacology
Substances
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1-(2-fluoroethyl)-4-(4-N,N-dimethylaminostyryl)-1H-1,2,3-triazole
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1-(4-(3-fluoropropoxy)styryl)-3,5-dimethoxybenzene
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Amyloid beta-Peptides
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Aniline Compounds
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Fluorine Radioisotopes
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Peptide Fragments
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Radiopharmaceuticals
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Stilbenes
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Styrenes
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Triazoles
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amyloid beta-protein (1-42)
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Resveratrol