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F-18 Stilbenes as PET Imaging Agents for Detecting β-Amyloid Plaques in the Brain

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Departments of Radiology and Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, and Department of Neuroscience, AstraZeneca, Wilmington, Delaware 19850
Cite this: J. Med. Chem. 2005, 48, 19, 5980–5988
Publication Date (Web):August 23, 2005
Copyright © 2005 American Chemical Society

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    Imaging agents targeting β-amyloid (Aβ) may be useful for diagnosis and treatment of patients with Alzheimer's disease (AD). Compounds 3e and 4e are fluorinated stilbene derivatives displaying high binding affinities for Aβ plaques in AD brain homogenates (Ki = 15 ± 6 and 5.0 ± 1.2 nM, respectively). In vivo biodistributions of [18F]3e and [18F]4e in normal mice exhibited excellent brain penetrations (5.55 and 9.75% dose/g at 2 min), and rapid brain washouts were observed, especially for [18F]4e (0.72% dose/g at 60 min). They also showed in vivo plaque labeling in APP/PS1 or Tg2576 transgenic mice, animal models for AD. Autoradiography of postmortem AD brain sections and AD homogenate binding studies confirmed the selective and specific binding properties to Aβ plaques. In conclusion, the preliminary results strongly suggest that these fluorinated stilbene derivatives, [18F]3e and [18F]4e, are suitable candidates as Aβ plaque imaging agents for studying patients with AD.

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     Department of Radiology, University of Pennsylvania.



     Hank F. Kung, Ph.D., Department of Radiology, University of Pennsylvania, 3700 Market St., Rm. 305, Philadelphia, PA 19104. Tel:  (215)662-3096, Fax:  (215)349-5035; e-mail:  kunghf@


     Department of Pharmacology, University of Pennsylvania.

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