Report of the National Heart, Lung, and Blood Institute Working Group on the Translation of Cardiovascular Molecular Imaging

Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute/National Institutes of Health, 6701 Rockledge Dr, Room 8216, Bethesda, MD 20892, USA.
Circulation (Impact Factor: 14.43). 05/2011; 123(19):2157-63. DOI: 10.1161/CIRCULATIONAHA.110.000943
Source: PubMed
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Available from: Denis B Buxton
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    • "At present, it is difficult for physicians to specifically detect and quantify plaque lesion buildup in vessel walls. Cardiovascular magnetic resonance (CMR) is one of several techniques being investigated to identify plaque burden in patients so that interventions can be conducted before rupture occurs [1,2]. We have used novel gadolinium (Gd)-containing C80 endohedrals (Trimetaspheres™, TMS, Gd3N@C80) [3] as a platform to develop new atherosclerotic targeting contrast agents (ATCA) for CMR. "
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    ABSTRACT: Background The hallmark of atherosclerosis is the accumulation of plaque in vessel walls. This process is initiated when monocytic cells differentiate into macrophage foam cells under conditions with high levels of atherogenic lipoproteins. Vulnerable plaque can dislodge, enter the blood stream, and result in acute myocardial infarction and stroke. Imaging techniques such as cardiovascular magnetic resonance (CMR) provides one strategy to identify patients with plaque accumulation. Methods We synthesized an atherosclerotic-targeting contrast agent (ATCA) in which gadolinium (Gd)-containing endohedrals were functionalized and formulated into liposomes with CD36 ligands intercalated into the lipid bilayer. In vitro assays were used to assess the specificity of the ATCA for foam cells. The ability of ATCA to detect atherosclerotic plaque lesions in vivo was assessed using CMR. Results The ATCA was able to detect scavenger receptor (CD36)-expressing foam cells in vitro and were specifically internalized via the CD36 receptor as determined by focused ion beam/scanning electron microscopy (FIB-SEM) and Western blotting analysis of CD36 receptor-specific signaling pathways. The ATCA exhibited time-dependent accumulation in atherosclerotic plaque lesions of ApoE −/− mice as determined using CMR. No ATCA accumulation was observed in vessels of wild type (C57/b6) controls. Non-targeted control compounds, without the plaque-targeting moieties, were not taken up by foam cells in vitro and did not bind plaque in vivo. Importantly, the ATCA injection was well tolerated, did not demonstrate toxicity in vitro or in vivo, and no accumulation was observed in the major organs. Conclusions The ATCA is specifically internalized by CD36 receptors on atherosclerotic plaque providing enhanced visualization of lesions under physiological conditions. These ATCA may provide new tools for physicians to non-invasively detect atherosclerotic disease.
    Full-text · Article · Jan 2013 · Journal of Cardiovascular Magnetic Resonance
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    ABSTRACT: The high mortality rate of diseases of the aorta has its foundation in imaging methods that define anatomy and disease burden but less so upon the diagnosis of asymptomatic conditions, rate of aneurysm expansion, or prediction of rupture. However, anatomical features can now be co-localized with molecular and physiological activity. The advancement of nanoparticles based upon iron oxide will also serve to bring a trio of magnetic, radionuclide, and optical imaging modalities together. The combinations of these technologies are still at the preclinical refinement stage but already enzyme-activatable probes have been used to interrogate different stages of aneurysmal disease. Like many disease areas where in vivo optical imaging may play a major role in the future, unravelling and management of aortic aneurysmal disease will progress through better understanding of its pathophysiology. This will translate into new clinical applications led by target-specific probes and the use of nanoparticle technology.
    No preview · Article · Feb 2011 · Current Cardiovascular Imaging Reports
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    ABSTRACT: Every year nearly 1 million Americans with myocardial infarction suffer from acute coronary syndromes. Despite advances in reperfusion therapy, these molecular events may often lead to ventricular adverse remodeling resulting in the heart failure. This observation became a driving force to develop noninvasive imaging strategies to evaluate remodeling using concepts of molecular imaging. As such, cardiovascular imaging plays an important role in shifting the paradigm from the disease treatment to early diagnosis, prognostication, and stratification, which has a tremendous potential to alleviate socioeconomic and health care costs associated with the treatment of heart failure patients. This review is intended to be a brief overview of recent nuclear imaging techniques and applications to assess molecular events associated with the process of left ventricular (LV) remodeling following myocardial infarction (MI). The specific approaches presented here will include imaging of perfusion, viability, metabolism, cardiac neuroreceptors, angiogenesis, proteases activity, and renin-angiotensin-aldosterone system activation. We will first describe basic concepts of molecular imaging, then we will provide an overview of recent advances in molecular imaging technology, and finally we will report current nuclear imaging strategies in assessment of LV remodeling. The emphasis will be put on radiotracer-based modalities including single photon emission computed tomography (SPECT) and positron emission tomography (PET) techniques, although other clinical imaging modalities will be also briefly discussed. We expect that in near future these targeted imaging approaches will complement standard physiological parameters and will play a crucial role in post-MI patients’ stratification and development of individual therapy regimes.
    No preview · Article · Jun 2012 · Current Cardiovascular Imaging Reports
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