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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: September 1, 2011.

Chemical name:5-(5-(2-(2-(2-[18F]Fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N-methylpyridin-2-amineimage 124771896 in the ncbi pubchem database
Abbreviated name:[18F]FPYBF-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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Alzheimer's disease (AD) is a form of dementia with a gradual memory loss and a progressive decline in mental functions over time (1, 2). It is characterized pathologically by neuronal loss, extracellular senile plaques (aggregates of amyloid-β peptides consisting of 40–42 amino acids), and intracellular neurofibrillary tangles (filaments of microtubule-binding hyperphosphorylated protein tau) in the brain, especially in the hippocampus and associative regions of the cortex (3, 4). β-Amyloid peptides and tau proteins 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 β-amyloid imaging agents have been developed for magnetic resonance imaging (MRI), single-photon emission computed tomography, and positron emission tomography (PET) (8-13) as measures of the presence of plaque. 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. Of these analogs, 2-(1-(6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl)ethylidene)malono nitrile ([18F]FDDNP) was studied in humans, and it showed more binding in the brains of patients with AD than in those of healthy people (14). However, [18F]FDDNP showed low signal/noise ratios for PET imaging because it is highly lipophilic. N-Methyl-[11C]-2-(4’-methylaminophenyl)-6-hydroxybenzothiasole, a β-amyloid binding compound based on a series of neutral thioflavin-T derivatives (15), was radiolabeled with the positron-emitting radionuclide 11C ([11C]6-OH-BTA-1 or [11C]PIB). [11C]6-OH-BTA-1 was found to be a promising imaging agent for senile plaques in the brain (10). 5-(5-(2-(2-(2-[18F]Fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N,N-dimethylpyridin-2-amine benzenamine ([18F]FPYBF-1) was found to exhibit good initial uptake but slow washout from the brain in normal mice, and thus it is not suitable for imaging studies. Ono et al. (16) reported the development of the less lipophilic monomethylamino derivative of [18F]FPHBF-1, 5-(5-(2-(2-(2-[18F]fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N-methylpyridin-2-amine ([18F]FPYBF-2) as a PET imaging agent for β-amyloid plaques in the brain.



[18F]FPYBF-2 was readily synthesized by standard 18F-fluorination of the N-BOC–protected mesylate derivative with [18F]KF/Kryptofix 2.2.2, for 5 min at 120°C and the subsequent acid hydrolysis with 10% HCl for 5 min at 120°C (16). [18F]FPYBF-2 was purified with high-performance liquid chromatography. Overall radiochemical yield was 52%, with a specific activity of 242 GBq/µmol (6.5 Ci/µmol) at the end of synthesis and a radiochemical purity of >99%. Total synthesis time was not reported. CLogP (lipophilicity) values were calculated to be 2.94 and 3.73 for [18F]FPYBF-2 and [18F]FPYBF-1, respectively.

In Vitro Studies: Testing in Cells and Tissues


FPYBF-2 has a binding affinity (Ki) value of 3.85 ± 0.23 nM for aggregated β-amyloid(1–42) peptide in competition with [125I]IMPY (16). [18F]FPYBF-2 bound to the cortex of post-mortem AD brain slices but not to control brain slices as visualized with in vitro autoradiography studies. The brains showed a distinctive labeling of β-amyloid plaques by co-staining with thioflavin-S. No such labeling and staining were observed in the control wild-type mice. No blocking studies were performed.

Animal Studies



[18F]FPYBF-2 (0.37 MBq (10 μCi)) was injected intravenously into normal male mice (n = 5/group) to study its accumulation in the brain and other organs/tissues at 2, 10, 30, and 60 min after injection (16). [18F]FPYBF-2 showed rapid penetration into the brain with 7.38 ± 0.84% injected dose (ID)/g at 2 min and a quick washout (3.15 ± 0.10% ID/g at 60 min). The brain2min/brain60min value was 2.34. In comparison, [18F]FPYBF-1 exhibited a brain2min/brain60min value of 2.11, which was slightly lower than that of [18F]FPYBF-2. The organs with the highest accumulation at 60 min after injection were the intestine (30.9% ID/g) and stomach (22.5% ID/g), followed by the liver (8.71% ID/g), kidney (3.70% ID/g), lung (2.88% ID/g), and heart (2.60% ID/g). The radioactivity levels at 60 min were 2.42% ID/g and 1.72% ID/g in the blood and bone, respectively. The bone radioactivity was 2.65% ID/g at 2 min. Ex vivo autoradiography studies of the brains of transgenic Tg2576 mice overexpressing β-amyloid plaques in the brain were performed after injection of [18F]FPYBF-2. The brains showed a distinctive labeling of β-amyloid plaques and co-staining with thioflavin-S. No such labeling and staining were observed in the control wild-type mice. No blocking studies were performed.

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


No publication is currently available.

Human Studies


No publication is currently available.


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