Comparison of Synthetic High Density Lipoprotein (HDL) Contrast Agents for MR Imaging of Atherosclerosis

Cormode, David P.; Chandrasekar, Rohith; Delshad, Amanda; Briley‐Saebo, Karen C.; Calcagno, Claudia; Barazza, Alessandra; Mulder, Willem J. M.; Fisher, Edward A.; Fayad, Zahi A.

doi:10.1021/bc800520d

Cited by 65 publications

(61 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 500 mg/kg (2.53 mmol of gold per kilogram of body weight) dose of Au-HDL used is comparable to that used for commercially available iodinated contrast agents (370 mg/kg or 2.92 mmol of iodine per kilogram of body weight) ( 13 ). We chose a dose equivalent to the number of particles used in our previous MR imaging studies with high-density lipoprotein-based contrast agents ( 22,37 ). Nevertheless, we plan to perform dose-response studies to determine optimized dosing.…”

Section: Experimental Studies: Multicolor Ct Evaluation Of Atherosclementioning

confidence: 99%

Atherosclerotic Plaque Composition: Analysis with Multicolor CT and Targeted Gold Nanoparticles

Cormode

Roessl²,

Thran³

et al. 2010

Radiology

Self Cite

438

364

View full text Add to dashboard Cite

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, calcifi cation, 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. Au-HDL, an iodine-based contrast agent, and calcium phosphate were imaged in a variety of phantoms. Apolipoprotein E knockout (apo E-KO) mice were used as the model for atherosclerosis. Gold nanoparticles targeted to atherosclerosis (Au-HDL) were intravenously injected at a dose of 500 mg per kilogram of body weight. Iodine-based contrast material was injected 24 hours later, after which the mice were imaged. Wild-type mice were used as controls. Macrophage targeting by Au-HDL was further evaluated by using transmission electron microscopy and confocal microscopy of aorta sections. Results:Multicolor CT enabled differentiation of Au-HDL, iodinebased contrast material, and calcium phosphate in the phantoms. Accumulations of Au-HDL were detected in the aortas of the apo E-KO mice, while the iodine-based contrast agent and the calcium-rich tissue could also be detected and thus facilitated visualization of the vasculature and bones (skeleton), respectively, during a single scanning examination. Microscopy revealed Au-HDL to be primarily localized in the macrophages on the aorta sections; hence, the multicolor CT images provided information about the macrophage burden. Conclusion:Spectral CT used with carefully chosen contrast agents may yield valuable information about atherosclerotic plaque composition.q RSNA, 2010Supplemental material: http://radiology.rsna.org/lookup /suppl

show abstract

Section: Experimental Studies: Multicolor Ct Evaluation Of Atherosclementioning

confidence: 99%

Atherosclerotic Plaque Composition: Analysis with Multicolor CT and Targeted Gold Nanoparticles

Cormode

Roessl²,

Thran³

et al. 2010

Radiology

Self Cite

438

364

View full text Add to dashboard Cite

show abstract

“…The new formulation produced greater contrast than the original HDL formulation also in the MRI images of aortas of ApoE−/− mice, indicating that the P2A2 peptide maintains the same enhanced effect in vivo. A new artificial HDL-based platform, labeled with MRI and Optical agents, has been recently developed using synthetic peptides (37pA) instead of natural ApoA-I [18]. This approach could have the advantage of avoiding the use of plasma derived products and must be more suitable for a clinical translation.…”

Section: High Density Lipoproteins (Hdl)mentioning

confidence: 99%

Lipid-Based Nanoparticles in Cardiovascular Molecular Imaging

Crich

Alberti

Orio

et al. 2012

Curr Cardiovasc Imaging Rep

View full text Add to dashboard Cite

Abstract.The Gd(III) complexes currently used as MRI contrast agents are hydrophilic agents that distribute in the vascular and extracellular compartments. The visualization of atherosclerotic plaques requires systems endowed with lipophilic characteristics. Several Gd(III) complexes bearing lipophilic substituents have been reported. Among them Gd(III) complexes containing one or two aliphatic chains appears particularly useful for the intended application. These amphiphilic Gd(III) complexes have been incorporated into various type of supramolecular adducts that ensure enough sensibility for their detection in MR images of atherosclerotic plaques. Much attention has been devoted to the use of HDL and LDL Gd-loaded particles. The presence of long aliphatic chain(s) promotes the spontaneous aggregation of these complexes to form micelles that may associate as such to the surface of HDL particles. It has been shown that the transfer of single amphiphilic complexes into the lipidic core of the particles is possible by de-assembling the micelles through the formation of "host-guest" adducts with cyclodextrin. Gd-loaded liposomes have also been successfully tested in plaque detection as well as perfluoronanoparticles loaded with CEST agents. 4Introduction.

show abstract

“…Similarly, solid lipid NPs (SLNs) loaded with CdSe/ZnS QDs were shown to be biocompatible [35]. Other NPs, such as high-density lipoproteins (HDL) end up mainly in liver and to a lesser extent in spleen, and are barely detectable in heart, lungs, and kidneys [36].…”

Section: Nanoparticle Toxicity Considerationsmentioning

confidence: 99%

Nanoparticle-based drug delivery: case studies for cancer and cardiovascular applications

Galvin

Thompson

Ryan

et al. 2011

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Nanoparticles (NPs) comprised of nanoengineered complexes are providing new opportunities for enabling targeted delivery of a range of therapeutics and combinations. A range of functionalities can be included within a nanoparticle complex, including surface chemistry that allows attachment of cell-specific ligands for targeted delivery, surface coatings to increase circulation times for enhanced bioavailability, specific materials on the surface or in the nanoparticle core that enable storage of a therapeutic cargo until the target site is reached, and materials sensitive to local or remote actuation cues that allow controlled delivery of therapeutics to the target cells. However, despite the potential benefits of NPs as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of NP materials, as well as their size and shape. The need to validate each NP for safety and efficacy with each therapeutic compound or combination of therapeutics is an enormous challenge, which forces industry to focus mainly on those nanoparticle materials where data on safety and efficacy already exists, i.e., predominantly polymer NPs. However, the enhanced functionality affordable by inclusion of metallic materials as part of nanoengineered particles provides a wealth of new opportunity for innovation and new, more effective, and safer therapeutics for applications such as cancer and cardiovascular diseases, which require selective targeting of the therapeutic to maximize effectiveness while avoiding adverse effects on non-target tissues.

show abstract

Comparison of Synthetic High Density Lipoprotein (HDL) Contrast Agents for MR Imaging of Atherosclerosis

Cited by 65 publications

References 29 publications

Atherosclerotic Plaque Composition: Analysis with Multicolor CT and Targeted Gold Nanoparticles

Atherosclerotic Plaque Composition: Analysis with Multicolor CT and Targeted Gold Nanoparticles

Lipid-Based Nanoparticles in Cardiovascular Molecular Imaging

Nanoparticle-based drug delivery: case studies for cancer and cardiovascular applications

Contact Info

Product

Resources

About