Magnetic resonance molecular imaging of post‐stroke neuroinflammation with a P‐selectin targeted iron oxide nanoparticle

Jin, Albert; Tuor, Ursula I.; Rushforth, David; Filfil, Rana; Kaur, Jasbinder; Ni, Feng; Tomanek, Bogusław; Barber, Philip A.

doi:10.1002/cmmi.292

Cited by 46 publications

(33 citation statements)

References 30 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…fucoidan, antibodies, sialyl Lewis X ) (Jin et al, 2009;McAteer et al, 2012;Beziere et al, 2014;Farr et al, 2014;Li et al, 2014). In a stroke/neuroinflammation context, Pselectin has been targeted in molecular MRI studies, with disappointing results: P-selectin targeted USPIOs (ultrasmall particles of iron oxide) had a limited sensitivity and specificity in a mouse ischaemic stroke model (Jin et al, 2009) and a dual antibody-conjugated MPIOs, targeting both VCAM1 and P-selectin, did not show better images over single VCAM1 antibody-conjugated MPIOs in a model of acute inflammation in mice . More recently, sialyl Lewis X -conjugated silica iron nanoparticles have been tested in a rodent stroke model.…”

Section: Discussionmentioning

confidence: 99%

Molecular magnetic resonance imaging discloses endothelial activation after transient ischaemic attack

Quenault

Lizarrondo

Etard

et al. 2016

Brain

View full text Add to dashboard Cite

About 20% of patients with ischaemic stroke have a preceding transient ischaemic attack, which is clinically defined as focal neurological symptoms of ischaemic origin resolving spontaneously. Failure to diagnose transient ischaemic attack is a wasted opportunity to prevent recurrent disabling stroke. Unfortunately, diagnosis can be difficult, due to numerous mimics, and to the absence of a specific test. New diagnostic tools are thus needed, in particular for radiologically silent cases, which correspond to the recommended tissue-based definition of transient ischaemic attack. As endothelial activation is a hallmark of cerebrovascular events, we postulated that this may also be true for transient ischaemic attack, and that it would be clinically relevant to develop non-invasive in vivo imaging to detect this endothelial activation. Using transcriptional and immunohistological analyses for adhesion molecules in a mouse model, we identified brain endothelial P-selectin as a potential biomarker for transient ischaemic attack. We thus developed ultra-sensitive molecular magnetic resonance imaging using antibody-based microparticles of iron oxide targeting P-selectin. This highly sensitive imaging strategy unmasked activated endothelial cells after experimental transient ischaemic attack and allowed discriminating transient ischaemic attack from epilepsy and migraine, two important transient ischaemic attack mimics. We provide preclinical evidence that combining conventional magnetic resonance imaging with molecular magnetic resonance imaging targeting P-selectin might aid in the diagnosis of transient ischaemic attack.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular magnetic resonance imaging discloses endothelial activation after transient ischaemic attack

Quenault

Lizarrondo

Etard

et al. 2016

Brain

View full text Add to dashboard Cite

show abstract

“…Apart from radionuclide-based strategies, there have been a number of optical and MRI-based techniques developed for visualizing neuroinflammation, including the use of P-selectin targeted iron oxide nanoparticles for MRI imaging of early endothelial activation in poststroke inflammation (188), and the tracking of luciferase-expressing bone marrow cells via bioluminescence (4). The latter of these techniques involved the intravenous administration of luciferase-expressing bone marrow cells, known to differentiate into bone marrow-derived microglia after crossing the blood-brain barrier, induction of neuroinflammation via a stereotactic injection of lipopolysaccharide (LPS), and tracking of the luciferase-expressing bone marrow-derived microglia through a cranial window in a mouse head using bioluminescence.…”

Section: B Neurosciencementioning

confidence: 99%

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

James

Gambhir

2012

Physiological Reviews

925

954

View full text Add to dashboard Cite

Molecular imaging is revolutionizing the way we study the inner workings of the human body, diagnose diseases, approach drug design, and assess therapies. The field as a whole is making possible the visualization of complex biochemical processes involved in normal physiology and disease states, in real time, in living cells, tissues, and intact subjects. In this review, we focus specifically on molecular imaging of intact living subjects. We provide a basic primer for those who are new to molecular imaging, and a resource for those involved in the field. We begin by describing classical molecular imaging techniques together with their key strengths and limitations, after which we introduce some of the latest emerging imaging modalities. We provide an overview of the main classes of molecular imaging agents (i.e., small molecules, peptides, aptamers, engineered proteins, and nanoparticles) and cite examples of how molecular imaging is being applied in oncology, neuroscience, cardiology, gene therapy, cell tracking, and theranostics (therapy combined with diagnostics). A step-by-step guide to answering biological and/or clinical questions using the tools of molecular imaging is also provided. We conclude by discussing the grand challenges of the field, its future directions, and enormous potential for further impacting how we approach research and medicine.

show abstract

“…MNPs have been functionalized with peptides 5 and carbohydrates such as Sialyl Lewis X (SX). 1 Carbohydrate-functionalized MNPs can take advantage of clustering effects to achieve high binding affinities and specificities when compared to monovalent carbohydrate-protein interactions.…”

mentioning

confidence: 99%

Imaging Early Endothelial Inflammation Following Stroke by Core Shell Silica Superparamagnetic Glyconanoparticles That Target Selectin

et al. 2014

View full text Add to dashboard Cite

Activation of the endothelium is a pivotal first step for leukocyte migration into the diseased brain. Consequently, imaging this activation process is highly desirable. We synthesized carbohydrate-functionalized magnetic nanoparticles that bind specifically to the endothelial transmembrane inflammatory proteins E and P selectin. Magnetic resonance imaging revealed that the targeted nanoparticles accumulated in the brain vasculature following acute administration into a clinically relevant animal model of stroke, though increases in selectin expression were observed in both brain hemispheres. Nonfunctionalized naked particles also appear to be a plausible agent to target the ischemic vasculature. The importance of these findings is discussed regarding the potential for translation into the clinic.

show abstract

Magnetic resonance molecular imaging of post‐stroke neuroinflammation with a P‐selectin targeted iron oxide nanoparticle

Cited by 46 publications

References 30 publications

Molecular magnetic resonance imaging discloses endothelial activation after transient ischaemic attack

Molecular magnetic resonance imaging discloses endothelial activation after transient ischaemic attack

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

Imaging Early Endothelial Inflammation Following Stroke by Core Shell Silica Superparamagnetic Glyconanoparticles That Target Selectin

Contact Info

Product

Resources

About