MR molecular imaging of early endothelial activation in focal ischemia

Barber, Philip A.; Foniok, Tadeusz; Kirk, D.; Buchan, Alastair M.; Laurent, Sophie; Boutry, Sébastien; Müller, Robert N.; Hoyte, Lisa; Tomanek, Bogusław; Tuor, Ursula I.

doi:10.1002/ana.20162

Cited by 80 publications

(57 citation statements)

References 13 publications

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“…They are able to detect E-selectin on the 'blood side' of the blood-brain barrier, which is indicative of a lesion on the 'brain side'. The principle was shown for Gd-DTPA-B(sLe x m)A, which gave a modest signal enhancement for activated endothelium in the brain [45,46]. The aselective CA Gd-DTPA-BMA did not result in enhancement under the same conditions, showing that the blood-brain barrier was still intact.…”

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confidence: 86%

Glycoconjugate Probes and Targets for Molecular Imaging Using Magnetic Resonance

2010

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Review Molecular recognition of sugar residues applied in molecular imagingMolecular imaging aims at probing the molecular abnormalities that are the basis of diseases rather than to image their effects [1]. An important prerequisite of this approach is the selection of appropriate markers of disease and of targeting vectors to recognize them. The latter can include low-molecular weight substrates for enzymes or high-molecular weight affinity ligands, such as monoclonal antibodies, hormone analogs and recombinant proteins. Of the three major classes of biomolecules (proteins, nucleic acids and carbohydrates), the latter class is the least exploited in molecular imaging. However, a dense layer of glyco conjugates covers all cells and carbohydrate mediated cellular recognition plays an important role in nature, both in normal and malignant processes, such as cell-cell communication, infection, inflammation, metastasis and reproduction. As carriers of information, the carbohydrates have far greater potential than proteins and nucleic acids; three different nucleotides or amino acids can generate only six distinguishable structures, while over 1000 structures can be built up from three different monosaccharides [2]. This level of complexity is probably the reason for the fact that the exploration of these compounds in molecular imaging is lagging behind [3]. Recently, significant progress has been made in glycochemistry and glycobiology; for example, automated solid-phase synthesis of oligo saccharides has become possible [4], carbohydrate-based vaccines have been developed [5] and high-throughput methods have been designed for the screening of molecular interactions [6]. The exciting new developments in glycoscience are opening way for new challenges in exploring the full potential of carbohydrates in molecular imaging. Therefore, here we give an overview of the recent literature on the use of glycoconjugates either as probes or targets in molecular imaging using MRI.MRI contrast agents (CAs) are broadly described as positive or negative, depending on whether they give rise to a brightening or a darkening effect on the MR image, respectively. The positive or brightening effect predominantly relates to the longitudinal proton relaxation time (T 1 ) and the negative or darkening effect predominantly relates to the transverse proton relaxation time (T 2 ). To date, the majority of commercially available and clinically applied positive CAs are Gd 3+ complexes of the polyaminocarboxylates diethylene triamine pentacetic acid (DTPA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) (see FiguRe 1 for some typical examples) and negative CAs are various iron oxide particles. These agents are not actively targeting. The targeted CAs for application in molecular imaging that are currently under development and described below are generally based on compounds 1 (Gd-DTPA) and 2 (Gd-DOTA), as well as iron oxide nanoparticles.Glycoconjugate probes and targets for molecular imaging using magnetic resonanceRecently...

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Glycoconjugate Probes and Targets for Molecular Imaging Using Magnetic Resonance

2010

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“…7 Several sophisticated MR imaging modalities (eg, functional MR imaging, pharmacologic MR imaging, diffusion tensor imaging, molecular imaging) seem promising as novel tools for investigating many aspects of stroke. [9][10][11] The shortcomings of the intraluminal suture model and the thromboembolic occlusion model, that is, high variable cerebral lesion and high mortality rate, would hinder performing a longitudinal MR study to reveal the temporal evolution of ischemic lesion posttreatment on the same animals. Development of a stable focal cerebral ishemia model with high survival rate, where animals can be studied in a longer timeframe, is highly desirable for such in vivo longitudinal stroke studies.…”

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confidence: 99%

A Stable Focal Cerebral Ischemia Injury Model in Adult Mice: Assessment Using 7T MR Imaging

Zhang

Guo²,

Yang

et al. 2012

AJNR Am J Neuroradiol

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“…The feasibility of P-selectin imaging has been shown in the settings of early stage atherosclerosis using MRI (7,8). Furthermore, myocardial ischemia and reperfusion were assessed using molecular ultrasound imaging (9). However, methodologic problems remain.…”

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confidence: 99%

“…The agents used were based either on P-selectin-avid antibodies (10,11) or on synthetic analogs of Sialyl Lewis X (SLe X ), the natural ligand of P-selectin (7,8,10). Although the antibody-based agents generally yield good imaging results (9,11), the production of these tracers is expensive and time-consuming. The clinical potential of SLe X analogs, on the other hand, is limited by their poor imaging properties (7,8,10).…”

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confidence: 99%

“…Early detection of disease activity can result in earlier change of lifestyle and start of treatment, thereby reducing the risk of atherosclerotic complications. Identification of vulnerable plaques could guide clinical decision making and patient selection for preventative intervention, reducing the numbers that need to be treated (9). The superiority of a P-selectin imaging protocol over other imaging protocols for similar purposes, such as the apoptotic tracer 99m Tc-annexin A5 (13) and 18 F-FDG, is yet to be proven (14).…”

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confidence: 99%

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