Science to practice: versatile method to track transplanted encapsulated islet cells with multiple imaging modalities.

Pancreatic islet transplantation may provide an effective therapy for patients with type I diabetes. By encapsulating islets in alginate capsules, their survival is substantially improved. Methods to monitor the distribution of the encapsulated islets during delivery and afterward would help to optimize this type of therapy.

Monitoring of arterial wall remodelling in atherosclerotic rabbits with a magnetic resonance imaging contrast agent binding to matrix metalloproteinases.

Aims: P947 is a gadolinium-based magnetic resonance imaging (MRI) contrast agent with high affinity for several matrix metalloproteinases (MMPs) involved in arterial wall remodelling. We tested whether the intensity of enhancement detected in vivo in the arterial wall with P947 and MRI correlates with actual tissue MMP-related enzymatic activity measured in a rabbit atherosclerotic model subjected to dietary manipulations.

Methods And Results: Aortas of 15 rabbits in which atherosclerotic lesions were induced by balloon angioplasty and 4 months of hypercholesterolaemic diet were imaged at 'baseline' with P947-enhanced MRI.

Targeted iron oxide particles for in vivo magnetic resonance detection of atherosclerotic lesions with antibodies directed to oxidation-specific epitopes.

Objectives: The aim of this study was to determine whether iron oxide particles targeted to oxidation-specific epitopes image atherosclerotic lesions.

Background: Oxidized low-density lipoprotein plays a major role in atherosclerotic plaque progression and destabilization. Prior studies indicate that gadolinium micelles labeled with oxidation-specific antibodies allow for in vivo detection of vulnerable plaques with magnetic resonance imaging (MRI).

Quantum dot and Cy5.5 labeled nanoparticles to investigate lipoprotein biointeractions via Förster resonance energy transfer.

The study of lipoproteins, natural nanoparticles comprised of lipids and apolipoproteins that transport fats throughout the body, is of key importance to better understand, treat, and prevent cardiovascular disease. In the current study, we have developed a lipoprotein-based nanoparticle that consists of a quantum dot (QD) core and Cy5.5 labeled lipidic coating.

Recombinant high-density lipoprotein formulations.

High-density lipoprotein cholesterol (HDL-C) has emerged as a biomarker of residual cardiovascular disease (CVD) risk in high-risk patients treated with low-density lipoprotein cholesterol (LDL-C)-lowering therapies inclusive of inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA reductase. The evidence for increasing low levels of HDL-C is sparse, and the available data are confounded by metabolic interactions between elevated very low-density lipoprotein (VLDL) and LDL particle concentrations. Despite these limitations, there has been widespread interest in novel strategies that target HDL.

Multimodal clinical imaging to longitudinally assess a nanomedical anti-inflammatory treatment in experimental atherosclerosis.

Atherosclerosis is an inflammatory disease causing great morbidity and mortality in the Western world. To increase the anti-inflammatory action and decrease adverse effects of glucocorticoids (PLP), a nanomedicinal liposomal formulation of this drug (L-PLP) was developed and intravenously applied at a dose of 15 mg/kg PLP to a rabbit model of atherosclerosis. Since atherosclerosis is a systemic disease, emerging imaging modalities for assessing atherosclerotic plaque are being developed.

Nanoparticles as magnetic resonance imaging contrast agents for vascular and cardiac diseases.

Advances in nanoparticle contrast agents for molecular imaging have made magnetic resonance imaging a promising modality for noninvasive visualization and assessment of vascular and cardiac disease processes. This review provides a description of the various nanoparticles exploited for imaging cardiovascular targets. Nanoparticle probes detecting inflammation, apoptosis, extracellular matrix, and angiogenesis may provide tools for assessing the risk of progressive vascular dysfunction and heart failure.

The biological properties of iron oxide core high-density lipoprotein in experimental atherosclerosis.

Lipoproteins are a family of plasma nanoparticles responsible for the transportation of lipids throughout the body. High-density lipoprotein (HDL), the smallest of the lipoprotein family, measures 7-13 nm in diameter and consists of a cholesteryl ester and triglyceride core that is covered with a monolayer of phospholipids and apolipoproteins. We have developed an iron oxide core HDL nanoparticle (FeO-HDL), which has a lipid based fluorophore incorporated in the phospholipid layer.

Atherosclerotic plaque composition: analysis with multicolor CT and targeted gold nanoparticles.

Purpose: To investigate the potential of spectral computed tomography (CT) (popularly referred to as multicolor CT), used in combination with a gold high-density lipoprotein nanoparticle contrast agent (Au-HDL), for characterization of macrophage burden, calcification, and stenosis of atherosclerotic plaques.

Materials And Methods: The local animal care committee approved all animal experiments. A preclinical spectral CT system in which incident x-rays are divided into six different energy bins was used for multicolor imaging.

Reproducibility of black blood dynamic contrast-enhanced magnetic resonance imaging in aortic plaques of atherosclerotic rabbits.

Purpose: To investigate the short-term reproducibility of black-blood dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in atherosclerotic rabbits to evaluate the potential of this technique to be a reliable readout of plaque progression and/or regression upon therapeutic intervention.

Materials And Methods: Atherosclerotic rabbits were imaged at baseline and 24 hours later with DCE-MRI on a 1.5T MRI system.

Quantum dots for multimodal molecular imaging of angiogenesis.

Quantum dots exhibit unique optical properties for bioimaging purposes. We have previously developed quantum dots with a paramagnetic and functionalized coating and have shown their potential for molecular imaging purposes. In the current mini-review we summarize the synthesis procedure, the in vitro testing and, importantly, the in vivo application for multimodal molecular imaging of tumor angiogenesis.

Dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) of atherosclerotic plaque angiogenesis.

Atherosclerosis is a progressive systemic disease of the large arteries characterized by the formation of plaques in the vessel wall. Despite our knowledge of its pathogenesis, many vulnerable plaques still remain undiagnosed while in their asymptomatic phase and manifest for the first time with dramatic clinical events, such as stroke or myocardial infarction. In recent years, it is becoming clearer that sudden clinical events do not necessarily correlate with the degree of luminal obstruction caused by lesions, but rather with plaque composition.

Variations in atherosclerosis and remodeling patterns in aorta and carotids.

Background: Atherosclerosis is a progressive disease that causes vascular remodeling that can be positive or negative. The evolution of arterial wall thickening and changes in lumen size under current "standard of care" in different arterial beds is unclear. The purpose of this study was to examine arterial remodeling and progression/regression of atherosclerosis in aorta and carotid arteries of individuals at risk for atherosclerosis normalized over a 1-year period.

Magnetic resonance molecular imaging of thrombosis in an arachidonic acid mouse model using an activated platelet targeted probe.

Objective: Atherosclerotic plaque rupture leads to acute thrombus formation and may trigger serious clinical events such as myocardial infarction or stroke. Therefore, it would be valuable to identify atherothrombosis and vulnerable plaques before the onset of such clinical events. We sought to determine whether the noninvasive in vivo visualization of activated platelets was effective when using a target-specific MRI contrast agent to identify thrombi, hallmarks of vulnerable or high-risk atherosclerotic plaques.

RGD peptide functionalized and reconstituted high-density lipoprotein nanoparticles as a versatile and multimodal tumor targeting molecular imaging probe.

High density lipoprotein (HDL), an endogenous nanoparticle, transports fat throughout the body and is capable of transferring cholesterol from atheroma in the vessel wall to the liver. In the present study, we utilized HDL as a multimodal nanoparticle platform for tumor targeting and imaging via nonspecific accumulation and specific binding to angiogenically activated blood vessels. We reconstituted HDL (rHDL) with amphiphilic gadolinium chelates and fluorescent dyes.

Multifunctional imaging nanoprobes.

Multifunctional imaging nanoprobes have proven to be of great value in the research of pathological processes, as well as the assessment of the delivery, fate, and therapeutic potential of encapsulated drugs. Moreover, such probes may potentially support therapy schemes by the exploitation of their own physical properties, e.g.

Modified natural nanoparticles as contrast agents for medical imaging.

The development of novel and effective contrast agents is one of the drivers of the ongoing improvement in medical imaging. Many of the new agents reported are nanoparticle-based. There are a variety of natural nanoparticles known, e.

High-density lipoprotein-based contrast agents for multimodal imaging of atherosclerosis.

Lipoproteins, natural nanoparticles, have a well-recognized biological role and are highly suitable as a platform for delivering imaging agents. The ease with which both the exterior and interior of the particles can be modified permits the creation of multifunctional nanoparticles for imaging as well as the delivery of therapeutics. Importantly, their endogenous nature may make them biocompatible and biodegradable and allows them to avoid the recognition of the reticuloendothelial system.

Iron oxide core oil-in-water emulsions as a multifunctional nanoparticle platform for tumor targeting and imaging.

Nanoemulsions are increasingly investigated for the delivery of hydrophobic drugs to improve their bioavailability or make their administration possible. In the current study, oil-in-water emulsions with three different mean diameters (30, 60, and 95 nm) were developed as a new multimodality nanoparticle platform for tumor targeting and imaging. To that aim, hydrophobically coated iron oxide particles were included in the soybean oil core of the nanoemulsions to enable their detection with magnetic resonance imaging (MRI), while the conjugation of a near infrared fluorophore allowed optical imaging.

Multimodality imaging of atherosclerotic plaque activity and composition using FDG-PET/CT and MRI in carotid and femoral arteries.

Purpose: To evaluate the relationship between atherosclerotic plaque inflammation, as assessed by FDG-positron emission tomography/computed tomography (FDG-PET/CT), and plaque morphology and composition, as assessed by magnetic resonance imaging (MRI), in the carotid and femoral arteries.

Materials And Methods: Sixteen patients underwent FDG-PET/CT and MRI (T2-weighted (T2W) and proton density weighted (PDW)) of the carotid and femoral arteries. For every image slice, two observers determined the corresponding regions of the FDG-PET/CT and MRI image sets by matching CT and T2W axial images.

Quantification of inflammation within rabbit atherosclerotic plaques using the macrophage-specific CT contrast agent N1177: a comparison with 18F-FDG PET/CT and histology.

Unlabelled: Macrophages play a key role in atherosclerotic plaque rupture. The iodine-based contrast agent N1177 accumulates in macrophages, allowing for their detection with CT. In this study, we tested whether the intensity of enhancement detected with CT in the aortic wall of rabbits injected with N1177 correlated with inflammatory activity evaluated with (18)F-FDG PET/CT and macrophage density on histology.

Macrophage-specific lipid-based nanoparticles improve cardiac magnetic resonance detection and characterization of human atherosclerosis.

Objectives: We sought to determine whether gadolinium (Gd)-containing lipid-based nanoparticles (NPs) targeting the macrophage scavenger receptor-B (CD36) improve cardiac magnetic resonance (CMR) detection and characterization of human atherosclerosis.

Background: Gd-containing lipid-based NPs targeting macrophages have improved MR detection of murine atherosclerosis.

Methods: Gadolinium-containing untargeted NPs, anti-CD36 NPs, and nonspecific Fc-NPs were created.

Nanoparticulate assemblies of amphiphiles and diagnostically active materials for multimodality imaging.

Modern medicine has greatly benefited from recent dramatic improvements in imaging techniques. The observation of physiological events through interactions manipulated at the molecular level offers unique insight into the function (and dysfunction) of the living organism. The tremendous advances in the development of nanoparticulate molecular imaging agents over the past decade have made it possible to noninvasively image the specificity, pharmacokinetic profiles, biodistribution, and therapeutic efficacy of many novel compounds.