Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeting ?-amyloid plaques and oligomers: development of near-IR fluorescence imaging probes.

ABSTRACT: Evidence indicated that shifting treatment to a presymptomatic stage may produce significant benefits to prevent/alleviate the progression of Alzheimer's disease (AD); in particular, early incorporation of noninvasive imaging and biomarker testing will be significantly beneficial for AD drug development. Based on amyloid cascade hypothesis and its revised version, both ?-amyloid deposition and soluble oligomeric species could be good diagnostic biomarkers for AD. Near-IR fluorescence (NIRF) imaging, which so far is limited to animal studies, is a promising method for its incomparable advantages such as low cost, high-throughput and easy operation. This review focuses on recent reported NIRF probes that showed excellent binding to plaques and oligomers. We hope that this review will shed light on the future of NIRF probes' discovery.

SUBMITTER: Liu H

PROVIDER: S-EPMC6040043 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Targeting β-amyloid plaques and oligomers: development of near-IR fluorescence imaging probes.

Liu Hongwu H Yang Jian J Wang Letian L Xu Yungen Y Zhang Siyuan S Lv Jie J Ran Chongzhao C Li Yuyan Y

Future medicinal chemistry 20170127 2

Evidence indicated that shifting treatment to a presymptomatic stage may produce significant benefits to prevent/alleviate the progression of Alzheimer's disease (AD); in particular, early incorporation of noninvasive imaging and biomarker testing will be significantly beneficial for AD drug development. Based on amyloid cascade hypothesis and its revised version, both β-amyloid deposition and soluble oligomeric species could be good diagnostic biomarkers for AD. Near-IR fluorescence (NIRF) imag ...[more]

PMID: 28127995

Similar Datasets

Synthesis of Fluorescent Probes based on Stilbenes and Diphenylacetylenes targeting β-Amyloid Plaques.

Project description:Three fluorescent probes were synthesized aiming for optical imaging to detect amyloid plaques present in patients with Alzheimer's disease (AD). These compounds were prepared via Sonogashira coupling of a well-defined fluorophore (4-bora-3a, 4a-diaza s-indacene, BODIPY) with the pharmacophore possessing either a stilbene or a diphenylacetylene moiety. Different polyethylene glycol chain lengths were used as linkers between the fluorophore and the pharmacophore to adjust the lipophilicity of these probes. These compounds exhibit strong fluorescence emission between 665-680 nm and have very high extinction coefficients comparable to the parent fluorophore, BODIPY dye.

| S-EPMC2504756 | biostudies-literature

Near-Infrared Fluorescence Imaging of Carotid Plaques in an Atherosclerotic Murine Model.

Project description:Successful imaging of atherosclerosis, one of the leading global causes of death, is crucial for diagnosis and intervention. Near-infrared fluorescence (NIRF) imaging has been widely adopted along with multimodal/hybrid imaging systems for plaque detection. We evaluate two macrophage-targeting fluorescent tracers for NIRF imaging (TLR4-ZW800-1C and Feraheme-Alexa Fluor 750) in an atherosclerotic murine cohort, where the left carotid artery (LCA) is ligated to cause stenosis, and the right carotid artery (RCA) is used as a control. Imaging performed on dissected tissues revealed that both tracers had high uptake in the diseased vessel compared to the control, which was readily visible even at short exposure times. In addition, ZW800-1C's renal clearance ability and Feraheme's FDA approval puts these two tracers in line with other NIRF tracers such as ICG. Continued investigation with these tracers using intravascular NIRF imaging and larger animal models is warranted for clinical translation.

| S-EPMC8698491 | biostudies-literature

Novel Benzofurans with (99m)Tc Complexes as Probes for Imaging Cerebral ?-Amyloid Plaques.

Project description:Two novel benzofuran derivatives coupled with (99m)Tc complexes were tested as probes for imaging cerebral ?-amyloid plaques using single photon emission tomography. Although both derivatives bound to A?(1-42) aggregates, (99m)Tc-BAT-BF showed higher affinity than (99m)Tc-MAMA-BF. In sections of brain tissue from an animal model of AD, (99m)Tc-BAT-BF clearly labeled ?-amyloid plaques. In biodistribution experiments using normal mice, (99m)Tc-BAT-BF displayed high uptake soon after its injection and washed out from the brain rapidly, a highly desirable feature for an imaging agent. (99m)Tc-BAT-BF may be a potential probe for imaging ?-amyloid plaques in Alzheimer's brains.

| S-EPMC4007700 | biostudies-literature

RNA aptamer probes as optical imaging agents for the detection of amyloid plaques.

Project description:Optical imaging using multiphoton microscopy and whole body near infrared imaging has become a routine part of biomedical research. However, optical imaging methods rely on the availability of either small molecule reporters or genetically encoded fluorescent proteins, which are challenging and time consuming to develop. While directly labeled antibodies can also be used as imaging agents, antibodies are species specific, can typically not be tagged with multiple fluorescent reporters without interfering with target binding, and are bioactive, almost always eliciting a biological response and thereby influencing the process that is being studied. We examined the possibility of developing highly specific and sensitive optical imaging agents using aptamer technology. We developed a fluorescently tagged anti-Aβ RNA aptamer, β55, which binds amyloid plaques in both ex vivo human Alzheimer's disease brain tissue and in vivo APP/PS1 transgenic mice. Diffuse β55 positive halos, attributed to oligomeric Aβ, were observed surrounding the methoxy-XO4 positive plaque cores. Dot blots of synthetic Aβ aggregates provide further evidence that β55 binds both fibrillar and non-fibrillar Aβ. The high binding affinity, the ease of probe development, and the ability to incorporate multiple and multimodal imaging reporters suggest that RNA aptamers may have complementary and perhaps advantageous properties compared to conventional optical imaging probes and reporters.

| S-EPMC3935954 | biostudies-literature

Indocyanine green enables near-infrared fluorescence imaging of lipid-rich, inflamed atherosclerotic plaques.

Project description:New high-resolution molecular and structural imaging strategies are needed to visualize high-risk plaques that are likely to cause acute myocardial infarction, because current diagnostic methods do not reliably identify at-risk subjects. Although molecular imaging agents are available for low-resolution detection of atherosclerosis in large arteries, a lack of imaging agents coupled to high-resolution modalities has limited molecular imaging of atherosclerosis in the smaller coronary arteries. Here, we have demonstrated that indocyanine green (ICG), a Food and Drug Administration-approved near-infrared fluorescence (NIRF)-emitting compound, targets atheromas within 20 min of injection and provides sufficient signal enhancement for in vivo detection of lipid-rich, inflamed, coronary-sized plaques in atherosclerotic rabbits. In vivo NIRF sensing was achieved with an intravascular wire in the aorta, a vessel of comparable caliber to human coronary arteries. Ex vivo fluorescence reflectance imaging showed high plaque target-to-background ratios in atheroma-bearing rabbits injected with ICG compared to atheroma-bearing rabbits injected with saline. In vitro studies using human macrophages established that ICG preferentially targets lipid-loaded macrophages. In an early clinical study of human atheroma specimens from four patients, we found that ICG colocalized with plaque macrophages and lipids. The atheroma-targeting capability of ICG has the potential to accelerate the clinical development of NIRF molecular imaging of high-risk plaques in humans.

| S-EPMC3112179 | biostudies-literature

PiB-Conjugated, Metal-Based Imaging Probes: Multimodal Approaches for the Visualization of ?-Amyloid Plaques.

Project description:In an effort toward the visualization of ?-amyloid plaques by in vivo imaging techniques, we have conjugated an optimized derivative of the Pittsburgh compound B (PiB), a well-established marker of A? plaques, to DO3A-monoamide that is capable of forming stable, noncharged complexes with different trivalent metal ions including Gd(3+) for MRI and (111)In(3+) for SPECT applications. Proton relaxivity measurements evidenced binding of Gd(DO3A-PiB) to the amyloid peptide A?1-40 and to human serum albumin, resulting in a two- and four-fold relaxivity increase, respectively. Ex vivo immunohistochemical studies showed that the DO3A-PiB complexes selectively target A? plaques on Alzheimer's disease human brain tissue. Ex vivo biodistribution data obtained for the (111)In-analogue pointed to a moderate blood-brain barrier (BBB) penetration in adult male Swiss mice (without amyloid deposits) with 0.36% ID/g in the cortex at 2 min postinjection.

| S-EPMC4027563 | biostudies-literature

RGD-conjugated two-photon absorbing near-IR emitting fluorescent probes for tumor vasculature imaging.

Project description:Observation of the activation and inhibition of angiogenesis processes is important in the progression of cancer. Application of targeting peptides, such as a small peptide that contains adjacent L-arginine (R), glycine (G) and L-aspartic acid (D) residues can afford high selectivity and deep penetration in vessel imaging. To facilitate deep tissue vasculature imaging, probes that can be excited via two-photon absorption (2PA) in the near-infrared (NIR) and subsequently emit in the NIR are essential. In this study, the enhancement of tissue image quality with RGD conjugates was investigated with new NIR-emitting pyranyl fluorophore derivatives in two-photon fluorescence microscopy. Linear and nonlinear photophysical properties of the new probes were comprehensively characterized; significantly the probes exhibited good 2PA over a broad spectral range from 700-1100 nm. Cell and tissue images were then acquired and examined, revealing deep penetration and high contrast with the new pyranyl RGD-conjugates up to 350 μm in tumor tissue.

| S-EPMC4627496 | biostudies-literature

B,O-chelated azadipyrromethenes as near-IR probes.

Project description:Complementary synthetic routes to a new class of near-IR fluorophores are described. These allow facile access (four synthetic steps) to the core fluorophore and substituted derivatives with emissions between 740 and 780 nm in good quantum yields.

| S-EPMC2631357 | biostudies-literature

Synthesis of biphenyltrienes as probes for beta-amyloid plaques.

Project description:We report a series of p-hydroxy-, p-amino-, p-monomethylamino-, and p-monofluoroethylamino-substituted biphenyltrienes that displayed high binding affinities to beta-amyloid plaques. In an in vitro binding assay using postmortem brain homogenates of Alzheimer's patients and [(125)I]9, the triene compounds showed excellent binding affinities. When labeled with suitable radionuclides, they are useful as in vivo imaging agents for detecting Abeta plaques in the brains of Alzheimer's patients.

| S-EPMC2597440 | biostudies-literature

Development of fluorescence imaging probes for nicotinic acetylcholine α4β2∗ receptors.

Project description:Nicotinic acetylcholine α4β2∗ receptors (nAChRs) are implicated in various neurodegenerative diseases and smoking addiction. Imaging of brain high-affinity α4β2∗ nAChRs at the cellular and subcellular levels would greatly enhance our understanding of their functional role. Since better resolution could be achieved with fluorescent probes, using our previously developed positron emission tomography (PET) imaging agent [18F]nifrolidine, we report here design, synthesis and evaluation of two fluorescent probes, nifrodansyl and nifrofam for imaging α4β2∗ nAChRs. The nifrodansyl and nifrofam exhibited nanomolar affinities for the α4β2∗ nAChRs in [3H]cytisine-radiolabeled rat brain slices. Nifrofam labeling was observed in α4β2∗ nAChR-expressing HEK cells and was upregulated by nicotine exposure. Nifrofam co-labeled cell-surface α4β2∗ nAChRs, labeled with antibodies specific for a β2 subunit extracellular epitope indicating that nifrofam labels α4β2∗ nAChR high-affinity binding sites. Mouse brain slices exhibited discrete binding of nifrofam in the auditory cortex showing promise for examining cellular distribution of α4β2∗ nAChRs in brain regions.

| S-EPMC6004331 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data