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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD

Created: ; Last Update: March 5, 2007.

Chemical name:(E)-2-(2-(2-(2-[18F]Fluoroethoxy)ethoxy)ethoxy)-5-(4-dimethylaminostyryl)-pyridineimage 22417042 in the ncbi pubchem database
Abbreviated name:[18F]FPEGN3-Styrylpyridine, [18F]2
Agent category:Compound
Target:Amyloid-beta peptide
Target category:Acceptor
Method of detection:Positron emission tomography (PET)
Source of signal:18F
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Click on the above structure for additional information in PubChem.



Alzheimer's disease (AD) is a form of dementia with a gradual memory loss and a progressive decline in mental functions with time (1, 2). It is characterized pathologically by neuronal loss, extracellular amyloid-beta senile plaques (APs; aggregates of amyloid-beta peptides consisting of 40 to 42 amino acids) and intracellular neurofibrillary tangles (NFTs; filaments of microtubule-binding hyper-phosphorylated protein tau) in the brain, especially in the hippocampus and associative regions of the cortex (3, 4). Beta-amyloid peptides and tau protein are implicated as the main causes of neuronal degeneration and cell death (5, 6).

Early diagnosis of AD is important for treatment consideration and disease management (7). Various amyloid imaging agents have been developed for MRI, SPECT, and PET (8-13). The binding of different derivatives of Congo red, thioflavin, stibene, and aminonaphthalene has been studied in human post-mortem brain tissue and in transgenic mice. Out of these analogues, 2-(1-(6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malono nitrile ([18F]FDDNP) was first studied in humans, showing more binding in the brains of patients with AD than in those of healthy people (14). Despite of its slow clearance kinetics for PET imaging, [18F]FDDNP has been found to be a useful tool for detection of both NFTs and APs in AD patients. [11C]PIB, also known as Pittsburgh Compound B or [11C]6-OH-BTA-1, showed marked retention in brain cortices known to contain substantial amounts of APs. Other radioligands tested in humans were [11C]4-N-methylamino-4´-hydroxystilbene ([11C]SB-13, a stilbene derivative), and [125]IMPY (a pyridine derivative), which displayed a high accumulation in the frontal cortex in AD patients. (E)-2-(2-(2-(2-[18F]Fluoroethoxy)ethoxy)ethoxy)-5-(4-dimethylaminostyryl)-pyridine ([18F]FPEGN3-styrylpyridine) is a modified stilbene derivative, in which one of the benzene rings of stilbene was replaced with one pyridine ring (15). [18F]FPEGN3-styrylpyridine is being developed as a PET for amyloid plaque imaging.



Zhang et al. (15) prepared [18F]FPEGN3-styrylpyridine by [18F]fluoride nucleophilic displacement of the corresponding tosylate precursor in the presence of Kryptofix 2.2.2/K2CO3 with a high labeling yield (49-53%, decay-corrected) and a high radiochemical purity (>99%). Specific activity at the end of synthesis (50 min) was determined to be 41-54 GBq/mmol (1,500-2,000 Ci/mmol). [18F]FPEGN3-styrylpyridine showed adequate lipophilicity (log P = 3.22) for crossing the blood-brain barrier.

In Vitro Studies: Testing in Cells and Tissues


FPEGN3-styrylpyridine was reported to have high binding affinity (Ki = 2.5 ± 0.4) for β-amyloid plaques in homogenates of postmortem human AD brain membranes, using [125]IMPY as the radioligand (15). The binding affinity is similar to SB-13 (Ki = 1.2 ± 0.7) as previously reported (10). Furthermore, 8-10 fold higher specific binding of [18F]FPEGN3-styrylpyridine was detected in the gray matter than in white matter homogenates of AD brains, where β-amyloid plaques were low or nonexistent. The binding of [18F]FPEGN3-styrylpyridine to both gray and white matter from normal control brains was also low. In vitro autoradiography confirmed the binding of [18F]FPEGN3-styrylpyridine to discrete regions in the gray matter and not to the while matter of AD brain sections.

Animal Studies



[18F]FPEGN3-styrylpyridine (0.19-0.37 MBq, 5-10 μCi) was injected intravenously into normal mice (n = 3) to study its accumulation into the brain and other organs (15). The radioactivity in the excised brain samples was measured at 2, 30, 60 and 120 min after injection. [18F]FPEGN3-styrylpyridine showed a good accumulation in the brain with 7.77% ID/g at 2 min, 1.03% ID/g at 30 min, 1.28% ID/g at 60 min and 0.84% ID/g at 120 min. The liver and kidneys exhibited higher radioactivity accumulation than the brain at all time points. The radioactivity in the bone was 1.64% ID/g at 120 min, suggesting defluorination in mice.

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


No publication is currently available.

Human Studies


No publication is currently available.

NIH Support

AG022559, AG21868


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