Document Detail


11C-labeled stilbene derivatives as Abeta-aggregate-specific PET imaging agents for Alzheimer's disease.
MedLine Citation:
PMID:  12900282     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A series of stilbene derivatives as potential diagnostic imaging agents targeting amyloid plaques in Alzheimer's disease (AD) were synthesized and evaluated. The syntheses of the stilbenes were successfully achieved by a simple Wadsworth-Emmons reaction between diethyl (4-nitrobenzyl)phosphonate and 4-methoxybenzaldehyde. 4-N,N-dimethylamino-4'-methyoxy and the corresponding 4-N-monomethylamino-, 4'-hydroxy stilbenes showed good binding affinities towards Abeta aggregates in vitro (K(i) < 10 nM). The (11)C labeled 4-N-methylamino-4'-hydroxystilbene, [(11)C]4, was prepared by (11)C methylation of 4-amino-4'-hydroxystilbene. The [(11)C]4 displayed a moderate lipophilicity (log P = 2.36), and showed a very good brain penetration and washout from normal rat brain after an iv injection. In vitro autoradiography of transgenic AD mouse brain sections showed a high specific labeling of beta-amyloid plaques, whereas the control sections showed no binding. Taken together the data suggest that a relatively simple stilbene derivative, [(11)C]4, N-[(11)C]methylamino-4'-hydroxystilbene, may be useful as a positron emission tomography (PET) imaging agent for mapping Abeta plaques in the brain of patients with Alzheimer's disease.
Authors:
Masahiro Ono; Alan Wilson; Jose Nobrega; David Westaway; Paul Verhoeff; Zhi-Ping Zhuang; Mei-Ping Kung; Hank F Kung
Publication Detail:
Type:  Evaluation Studies; Journal Article    
Journal Detail:
Title:  Nuclear medicine and biology     Volume:  30     ISSN:  0969-8051     ISO Abbreviation:  Nucl. Med. Biol.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-08-05     Completed Date:  2004-05-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9304420     Medline TA:  Nucl Med Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  565-71     Citation Subset:  IM    
Affiliation:
Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / diagnosis*,  metabolism*
Amyloid beta-Protein / metabolism*
Animals
Autoradiography
Brain / metabolism*,  radionuclide imaging*
Carbon Radioisotopes / chemistry,  diagnostic use,  pharmacokinetics
Isotope Labeling / methods
Male
Mice
Mice, Transgenic
Radiopharmaceuticals / chemical synthesis,  diagnostic use,  pharmacokinetics
Rats
Rats, Sprague-Dawley
Stilbenes / diagnostic use*,  pharmacokinetics*
Tissue Distribution
Tomography, Emission-Computed / methods*
Chemical
Reg. No./Substance:
0/Amyloid beta-Protein; 0/Carbon Radioisotopes; 0/Radiopharmaceuticals; 0/Stilbenes

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  DNA vaccination: the answer to stable, protective T-cell memory?
Next Document:  Dimethylamino-fluorenes: ligands for detecting beta-amyloid plaques in the brain.