Aurones serve as probes of β-amyloid plaques in Alzheimer’s disease

Ono, Masahiro; Maya, Yoshifumi; Haratake, Mamoru; Ito, Kenyu; Mori, Hiroshi; Nakayama, Morio

doi:10.1016/j.bbrc.2007.06.162

Cited by 65 publications

(53 citation statements)

References 15 publications

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“…The binding affinity is in the same range as that of aurone derivatives possessing a nucleophilic group (NH 2 , NHMe, NMe 2 ). 47) These results clearly indicate that aurone derivatives exhibit considerable tolerance to structural modifications. The binding affinity of aurone derivatives is very close to that of known Ab imaging probes such as SB-13 (K i ϭ1.2 nM), 51) PIB (K i ϭ2.8 nM), 52) and IMPY (K i ϭ 1.4 nM), 51) indicating that they have sufficient affinity to test clinically.…”

Section: Aurone-based Ab B Imaging Probesmentioning

confidence: 86%

“…12). 47) To evaluate the binding affinity of aurone derivatives to Ab aggregates, a saturation assay with [ 125 I]40 was carried out using Ab(1-42) aggregates. When the saturation bindings of [ 125 I]40 were transformed to Scatchard plots, they showed linear plots, indicating that aurone derivatives have one binding site on Ab aggregates (Fig.…”

Section: Aurone-based Ab B Imaging Probesmentioning

confidence: 99%

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Development of Positron-Emission Tomography/Single-Photon Emission Computed Tomography Imaging Probes for in Vivo Detection of .BETA.-Amyloid Plaques in Alzheimer's Brains

Ono

2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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Section: Aurone-based Ab B Imaging Probesmentioning

confidence: 86%

Section: Aurone-based Ab B Imaging Probesmentioning

confidence: 99%

Development of Positron-Emission Tomography/Single-Photon Emission Computed Tomography Imaging Probes for in Vivo Detection of .BETA.-Amyloid Plaques in Alzheimer's Brains

Ono

2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Recently, we have reported that flavonoids including chalcone, flavone, and aurone serve as useful molecular scaffolds in the development of imaging agents for β-amyloid plaques in the brain [23][24][25][26][27][28] . Initially, we designed and synthesized four 99m Tc-labeled In the present study, to develop more useful 99m Tc imaging agents for the clinical diagnosis of AD, we synthesized two flavone and aurone derivatives with BAT as a chelation ligand.…”

Section: Ono Et Al 3/38mentioning

confidence: 99%

“…Based on this success, efforts were made to search for comparable 99m Tc imaging agents that target binding sites on -amyloid plaques in the brain of AD patients. Several 99m Tc-labeled imaging probes have been developed (Figure 1), but no clinical study of them has been reported [19][20][21][22] .Recently, we have reported that flavonoids including chalcone, flavone, and aurone serve as useful molecular scaffolds in the development of imaging agents for β-amyloid plaques in the brain [23][24][25][26][27][28] . Initially, we designed and synthesized four 99m Tc-labeled In the present study, to develop more useful 99m Tc imaging agents for the clinical diagnosis of AD, we synthesized two flavone and aurone derivatives with BAT as a chelation ligand.…”

mentioning

confidence: 99%

99mTc/Re complexes based on flavone and aurone as SPECT probes for imaging cerebral β-amyloid plaques

Ono

Ikeoka

Watanabe

et al. 2010

Bioorganic & Medicinal Chemistry Letters

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Two 99m Tc/Re complexes based on flavone and aurone were tested as potential probes for imaging -amyloid plaques using single photon emission computed tomography. Both 99m Tc-labeled derivatives showed higher affinity for A aggregates than did 99m Tc-BAT. In sections of brain tissue from an animal model of AD, the Re-flavone derivative 9 and Re-aurone derivative 19 intensely stained -amyloid plaques. In biodistribution experiments using normal mice, 99m Tc-labeled flavone and aurone displayed similar radioactivity pharmacokinetics. With additional modifications to improve their brain uptake, 99m Tc complexes based on the flavone or aurone scaffold may serve as probes for imaging cerebral -amyloid plaques Key words: Alzheimer's disease, -amyloid plaque, Tc-99m, single photon emission computed tomography (SPECT), imaging. Ono et al. 3/38Alzheimer's disease (AD) is a neurodegenerative disorder of the brain associated with irreversible cognititive decline, memory impairment, and behavioral changes.Currently, the only definitive confirmation of AD is by postmortem histopathological examination of -amyloid plaques in the brain. The early appraisal of clinical symptoms for a diagnosis of AD is often difficult and unreliable. Numerous reports suggest the accelerated accumulation of -amyloid plaques in the brain to be a key risk factor associated with AD. Consequently, the detection of individual -amyloid plaques in vivo by single photon emission tomography (SPECT) or positron emission tomography (PET) should improve the diagnosis of and also accelerate the discovery of effective therapeutic agents for AD [1][2][3][4] There are more SPECT scanners than PET imaging devices installed for routine clinical imaging, which provides a certain advantage to using SPECT imaging agents. Since SPECT is more valuable than PET in terms of routine diagnostic use, the development of more useful Aβ imaging agents for SPECT has been a critical issue. Although many radioiodinated SPECT imaging agents for detecting β-amyloid plaques have been reported, there are few reports on the development of 99m Tc imaging agents. Ono et al. 4/38 99m Tc (T 1/2 = 6.01 h, 141 keV) has become the most commonly used radionuclide in diagnostic nuclear medicine for several reasons: it is readily produced by an 99 Mo/ 99m Tc generator, the gamma-ray energy it emits is suitable for detection, and its physical half-life is compatible with the biological localization and residence time required for imaging. Its ready availability, essentially 24 h a day, and easiness of use make it the radionuclide of choice. New 99m Tc-labeled imaging agents will provide simple, convenient, and widespread SPECT-based imaging methods for detecting and eventually quantifying-amyloid plaques in living brain tissue.It has been reported that a dopamine transporter imaging agent, [ 99m Tc]TRODAT-1, is useful to detect the loss of dopamine neurons in the basal ganglia associated with Parkinson's disease. This is the first example of a 99m Tc imaging agent t...

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“…We have previously reported Aβ imaging agents based on flavonoid derivatives, such as flavones 15,16 , chalcones [17][18][19][20] , aurones 21,22 , and styrylchromones 23 studies demonstrated that chalcone derivatives fluoro-pegylated at the p-position of the 1-phenyl ring showed a sufficient brain uptake with a good binding capacity to Aβ plaques 19 . In addition, radioiodinated flavonoids, such as flavone and aurone derivatives, with a methoxy or oligoethyleneoxy group at the p-position of the 3-phenyl ring have the properties of high brain uptake and rapid clearance from the brain without significant decrease in the binding affinity for Aβ 15,22 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and evaluation of ethyleneoxylated and allyloxylated chalcone derivatives for imaging of amyloid β plaques by SPECT

Fuchigami¹,

Yamashita²,

Haratake³

et al. 2014

Bioorganic & Medicinal Chemistry

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Aurones serve as probes of β-amyloid plaques in Alzheimer’s disease

Cited by 65 publications

References 15 publications

Development of Positron-Emission Tomography/Single-Photon Emission Computed Tomography Imaging Probes for in Vivo Detection of .BETA.-Amyloid Plaques in Alzheimer's Brains

Development of Positron-Emission Tomography/Single-Photon Emission Computed Tomography Imaging Probes for in Vivo Detection of .BETA.-Amyloid Plaques in Alzheimer's Brains

99mTc/Re complexes based on flavone and aurone as SPECT probes for imaging cerebral β-amyloid plaques

Synthesis and evaluation of ethyleneoxylated and allyloxylated chalcone derivatives for imaging of amyloid β plaques by SPECT

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