| Dimethylamino-fluorenes: ligands for detecting beta-amyloid plaques in the brain. | |
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MedLine Citation:
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PMID: 12900283 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Formation of beta-amyloid (Abeta) plaques in the brain is a major contributing factor in the pathogenesis of Alzheimer's disease (AD). Detection of Abeta plaques in the brain will be potentially useful in early diagnosis and monitoring the progression of the disease. A series of novel Abeta aggregate-specific ligands based on fluorenes, which are simple and rigid tricyclic molecules, are synthesized and characterized. Starting with 2- or 3-aminofluorenes, 1a-1f, the amino group was converted to the N,N-dimethylamino group (2a-2f) in excellent yield. It was found that 7-iodo-2-N,N-dimethylaminofluorene (2f) showed an extremely high binding affinity to preformed Abeta40 aggregates (K(i) = 0.9 nM). In vitro autoradiography study using brain sections obtained from transgenic mice (Tg2576) with [(125)I]2f showed exquisitely high specific binding to Abeta plaques. The same section also displayed an equivalent labeling when stained by Thioflavin-S, a commonly used fluorescent dye for Abeta plaques. When [(125)I]2f was injected intravenously into normal mice, it exhibited an excellent brain uptake. Taken together the data suggest that [(125)I]2f may be useful as an in vivo imaging agent to detect Abeta plaques in the brain. |
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Authors:
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Chi-Wan Lee; Mei-Ping Kung; Catherine Hou; Hank F Kung |
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Publication Detail:
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Type: Comparative Study; Evaluation Studies; Journal Article; Research Support, U.S. Gov't, P.H.S.; Validation Studies |
Journal Detail:
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Title: Nuclear medicine and biology Volume: 30 ISSN: 0969-8051 ISO Abbreviation: Nucl. Med. Biol. Publication Date: 2003 Aug |
Date Detail:
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Created Date: 2003-08-05 Completed Date: 2004-05-17 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9304420 Medline TA: Nucl Med Biol Country: England |
Other Details:
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Languages: eng Pagination: 573-80 Citation Subset: IM |
Affiliation:
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Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alzheimer Disease
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diagnosis*,
metabolism* Amyloid beta-Protein / metabolism* Animals Autoradiography Brain / metabolism*, radionuclide imaging* Fluorenes / diagnostic use*, pharmacokinetics* Iodine Radioisotopes / diagnostic use, pharmacokinetics Isotope Labeling / methods Male Mice Mice, Inbred ICR Mice, Transgenic Organ Specificity Radiopharmaceuticals / chemical synthesis, diagnostic use, pharmacokinetics Tissue Distribution Tomography, Emission-Computed / methods* |
| Grant Support | |
ID/Acronym/Agency:
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NS 18509/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amyloid beta-Protein; 0/Fluorenes; 0/Iodine Radioisotopes; 0/Radiopharmaceuticals |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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