Abstract
In order to explore novel tau-imaging agents that can selectively detect neurofibrillary tangles in Alzheimer's disease (AD) brains, we designed and synthesized a series of heterocyclic phenylethenyl and (3-pyridinyl)ethenyl derivatives with or without a dimethyl amino group. In in vitro autoradiography using AD brain sections, all radioiodinated ligands with a dimethyl amino group bound to Aβ deposits in the sections. In contrast, the ligands without a dimethyl amino group showed different patterns of radioactivity accumulation in the sections depending on the kind of heterocycle contained in their molecules. Particularly, a phenylethenyl benzimidazole derivative ([(125)I]64) showed marked radioactivity accumulation in the temporal lobe which corresponded with the distribution of tau deposits. [(125)I]64 also showed the most favorable pharmacokinetics in normal mouse brains (3.69 and 0.06% ID/g at 2 and 60 min postinjection, respectively) among all ligands in this study. Taken together, these results suggest that [(123)I]64 may be a new candidate tau-imaging agent.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Alzheimer Disease / diagnostic imaging*
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Alzheimer Disease / metabolism
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Alzheimer Disease / pathology
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Amyloid beta-Peptides / metabolism
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Animals
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Autoradiography
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Benzimidazoles / chemical synthesis
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Benzimidazoles / chemistry*
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Benzimidazoles / pharmacokinetics
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Benzofurans / chemical synthesis
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Benzofurans / chemistry
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Benzofurans / pharmacokinetics
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Benzothiazoles / chemical synthesis
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Benzothiazoles / chemistry
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Benzothiazoles / pharmacokinetics
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Benzoxazoles / chemical synthesis
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Benzoxazoles / chemistry
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Benzoxazoles / pharmacokinetics
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Brain / diagnostic imaging*
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Brain / metabolism
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Brain / pathology
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Humans
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Iodine Radioisotopes
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Male
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Mice
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Neurofibrillary Tangles / diagnostic imaging*
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Neurofibrillary Tangles / metabolism
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Pyridines / chemical synthesis
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Pyridines / chemistry*
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Pyridines / pharmacokinetics
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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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Stereoisomerism
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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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Temporal Lobe / diagnostic imaging
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Temporal Lobe / metabolism
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Temporal Lobe / pathology
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Thiophenes / chemical synthesis
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Thiophenes / chemistry
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Thiophenes / pharmacokinetics
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tau Proteins / metabolism*
Substances
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6-iodo-2-styryl-1H-benzo(d)imidazole
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Amyloid beta-Peptides
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Benzimidazoles
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Benzofurans
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Benzothiazoles
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Benzoxazoles
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Iodine Radioisotopes
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Pyridines
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Radiopharmaceuticals
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Styrenes
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Thiophenes
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tau Proteins