F-18 Stilbenes as PET imaging agents for detecting β-amyloid plaques in the brain

被引:122
作者
Zhang, W
Oya, S
Kung, MP
Hou, C
Maier, DL
Kung, HF
机构
[1] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA
[3] AstraZeneca, Dept Neurosci, Wilmington, DE 19850 USA
关键词
D O I
10.1021/jm050166g
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Imaging agents targeting beta-amyloid (A beta) 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 A beta plaques in AD brain homogenates (K-i = 15 +/- 6 and 5.0 +/- 1.2 nM, respectively). In vivo biodistributions of [F-18]3e and [F-18]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 [F-18]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 A beta plaques. In conclusion, the preliminary results strongly suggest that these fluorinated stilbene derivatives, [F-18]3e and [(18F)]4e, are suitable candidates as A beta plaque imaging agents for studying patients with AD.
引用
收藏
页码:5980 / 5988
页数:9
相关论文
共 34 条
[1]   Binding characteristics of radiofluorinated 6-dialkylamino-2-naphthylethylidene derivatives as positron emission tomography imaging probes for β-amyloid plaques in Alzheimer's disease [J].
Agdeppa, ED ;
Kepe, V ;
Liu, J ;
Flores-Torres, S ;
Satyamurthy, N ;
Petric, A ;
Cole, GM ;
Small, GW ;
Huang, SC ;
Barrio, JR .
JOURNAL OF NEUROSCIENCE, 2001, 21 (24) :art. no.-RC189
[2]   Medicinal chemistry approaches for the treatment and prevention of Alzheimer disease [J].
Bachurin, SO .
MEDICINAL RESEARCH REVIEWS, 2003, 23 (01) :48-88
[3]   Amyloid β-protein (Aβ) assembly:: Aβ40 and Aβ42 oligomerize through distinct pathways [J].
Bitan, G ;
Kirkitadze, MD ;
Lomakin, A ;
Vollers, SS ;
Benedek, GB ;
Teplow, DB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (01) :330-335
[4]   Synthesis and evaluation of two 18F-labeled 6-iodo-2-(4′-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine derivatives as prospective radioligands for β-amyloid in Alzheimer's disease [J].
Cai, LS ;
Chin, FT ;
Pike, VW ;
Toyama, H ;
Liow, JS ;
Zoghbi, SS ;
Modell, K ;
Briard, E ;
Shetty, HU ;
Sinclair, K ;
Donohue, S ;
Tipre, D ;
Kung, MP ;
Dagostin, C ;
Widdowson, DA ;
Green, M ;
Gao, W ;
Herman, MM ;
Ichise, M ;
Innis, RB .
JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (09) :2208-2218
[5]   Natural oligomers of the amyloid-protein specifically disrupt cognitive function [J].
Cleary, JP ;
Walsh, DM ;
Hofmeister, JJ ;
Shankar, GM ;
Kuskowski, MA ;
Selkoe, DJ ;
Ashe, KH .
NATURE NEUROSCIENCE, 2005, 8 (01) :79-84
[6]   ANHYDROUS TETRABUTYLAMMONIUM FLUORIDE - A MILD BUT HIGHLY EFFICIENT SOURCE OF NUCLEOPHILIC FLUORIDE-ION [J].
COX, DP ;
TERPINSKI, J ;
LAWRYNOWICZ, W .
JOURNAL OF ORGANIC CHEMISTRY, 1984, 49 (17) :3216-3219
[7]  
Ginsberg S., 1999, Cerebral Cortex, P603
[8]   Medicine - The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics [J].
Hardy, J ;
Selkoe, DJ .
SCIENCE, 2002, 297 (5580) :353-356
[9]   Correlative memory deficits, A beta elevation, and amyloid plaques in transgenic mice [J].
Hsiao, K ;
Chapman, P ;
Nilsen, S ;
Eckman, C ;
Harigaya, Y ;
Younkin, S ;
Yang, FS ;
Cole, G .
SCIENCE, 1996, 274 (5284) :99-102
[10]   Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B [J].
Klunk, WE ;
Engler, H ;
Nordberg, A ;
Wang, YM ;
Blomqvist, G ;
Holt, DP ;
Bergström, M ;
Savitcheva, I ;
Huang, GF ;
Estrada, S ;
Ausén, B ;
Debnath, ML ;
Barletta, J ;
Price, JC ;
Sandell, J ;
Lopresti, BJ ;
Wall, A ;
Koivisto, P ;
Antoni, G ;
Mathis, CA ;
Långström, B .
ANNALS OF NEUROLOGY, 2004, 55 (03) :306-319