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

Buxton, Denis B.; Antman, Melissa; Danthi, Narasimhan; Dilsizian, Vasken; Fayad, Zahi A.; García, Mario J.; Jaff, Michael R.; Klimas, Michael; Libby, Peter; Nahrendorf, Matthias; Sinusas, Albert J.; Wickline, Samuel A.; Wu, Joseph C.; Bonow, Robert O.; Weissleder, Ralph

doi:10.1161/circulationaha.110.000943

Cited by 46 publications

(27 citation statements)

References 45 publications

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“…9 A wide range of medical imaging techniques have been proposed lately to characterize atherosclerotic plaques in vivo, starting with their morphological phenotyping 12,13 and continuing with more complex methods allowing the detection of molecular components. 14,15 The molecular imaging probes developed up-to-date are able to target an ample variety of vulnerability biomarkers involved in inflammation, thrombus formation, apoptosis, chemotaxis, angiogenesis, oxidative stress, collagen degradation, and so on. 14,15 Despite this explosive development of molecular imaging probes, their extrapolation into clinically available agents and techniques is largely delayed.…”

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confidence: 99%

“…14,15 The molecular imaging probes developed up-to-date are able to target an ample variety of vulnerability biomarkers involved in inflammation, thrombus formation, apoptosis, chemotaxis, angiogenesis, oxidative stress, collagen degradation, and so on. 14,15 Despite this explosive development of molecular imaging probes, their extrapolation into clinically available agents and techniques is largely delayed. 15 During our previous studies, 2 peptides were identified by phage display and used to target the vascular cell adhesion molecule-1 (VCAM-1), as a biomarker of inflammation (targeted with a cyclic heptapeptide: R832), 16 and phosphatidylserine, as a biomarker of apoptosis (targeted with a linear hexapeptide: R826).…”

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confidence: 99%

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Development of a Magnetic Resonance Imaging Protocol for the Characterization of Atherosclerotic Plaque by Using Vascular Cell Adhesion Molecule-1 and Apoptosis-Targeted Ultrasmall Superparamagnetic Iron Oxide Derivatives

Burtéa

Ballet

Laurent

et al. 2012

ATVB

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Objective— Acute ischemic events are often caused by the disruption of lipid-rich plaques, which are frequently not angiographically visible. Vascular cell adhesion molecule-1 and apoptotic cell-targeted peptides studied during our previous work were conjugated to ultrasmall superparamagnetic iron oxide (USPIO) (USPIO-R832 for vascular cell adhesion molecule-1 targeting; USPIO-R826 for apoptosis targeting) and assessed by magnetic resonance imaging. Methods and Results— Apolipoprotein E knockout mice were injected with 0.1 mmol Fe/kg body weight and were imaged on a 4.7-T Bruker magnetic resonance imaging until 24 hours after contrast agent administration. Aortic samples were then harvested and examined by histochemistry, and the magnetic resonance images and histological micrographs were analyzed with ImageJ software. The plaques enhanced by USPIO-R832 contained macrophages concentrated in the cap and a large necrotic core, whereas USPIO-R826 produced a negative enhancement of plaques rich in macrophages and neutral fats concentrated inside the plaque. Both USPIO derivatives colocalized with their target on histological sections and were able to detect plaques with a vulnerable morphology, but each one is detecting a specific environment. Conclusion— Our vascular cell adhesion molecule-1 and apoptotic cell targeted USPIO derivatives seem to be highly promising tools for atherosclerosis imaging contributing to the detection of vulnerable plaques. They are able to attain their target in low doses and as fast as 30 minutes after administration.

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confidence: 99%

Development of a Magnetic Resonance Imaging Protocol for the Characterization of Atherosclerotic Plaque by Using Vascular Cell Adhesion Molecule-1 and Apoptosis-Targeted Ultrasmall Superparamagnetic Iron Oxide Derivatives

Burtéa

Ballet

Laurent

et al. 2012

ATVB

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“…The application of non-invasive imaging technique in biodistribution studies is rapidly growing in both academic and industrial research. As shown in a recent report issued by the National Heart, Lung, and Blood Institute, publications on the application of molecular imaging for cardiovascular research has increased tenfold in the last 10 years (39).…”

Section: Non-invasive Imaging Technologies For Biodistribution and Pkmentioning

confidence: 99%

Challenges and Opportunities in Absorption, Distribution, Metabolism, and Excretion Studies of Therapeutic Biologics

Vugmeyster

2012

AAPS J

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Abstract. With the advancement of biotechnology in the last two decades, optimized and novel modalities and platforms of biologic moieties have emerged rapidly in drug discovery pipelines. In addition, new technologies for delivering therapeutic biologics (e.g., needle-free devices, nanoparticle complexes), as well as novel approaches for disease treatments (e.g., stem cell therapy, individualized medicine), continue to be developed. While pharmacokinetic studies are routinely carried out for therapeutic biologics, experiments that elucidate underlying mechanisms for clearance and biodistribution or identify key factors that govern absorption, distribution, metabolism, and excretion (ADME) of biologics often are not thoroughly conducted. Realizing the importance of biologics as therapeutic agents, pharmaceutical industry has recently begun to move the research focus from small molecules only to a blended portfolio consisting of both small molecules and biologics. This trend brings many opportunities for scientists working in the drug disposition research field. In anticipation of these opportunities and associated challenges, this review highlights impact of ADME studies on clinical and commercial success of biologics, with a particular focus on emerging applications and technologies and linkage with mechanistic pharmacokinetic/pharmacodynamic modeling and biomarker research.

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“…Although experimental studies like that of Broisat et al serve as "proof of principle," translation to humans will require overcoming barriers, including toxicology studies and the production of clinical-grade materials. 1 Ultimately, as with all biomarkers, imaging approaches to improving the management of patients at risk for atherosclerosis will require demonstration of clinical benefit and cost-effectiveness. Only multidisciplinary efforts will help us move the molecular imaging of atherosclerosis from the laboratory into the clinic.…”

Section: Article See P 927mentioning

confidence: 99%

“…1,2 In this issue of Circulation Research, Broisat et al 3 describe another step on the path toward noninvasive molecular imaging of inflammation in atherosclerotic plaque. Although still unproven, the early detection of trouble looming ahead could trigger steps for intervention, possibly involving the aggressive modulation of risk factors.…”

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confidence: 99%

Over a Hump for Imaging Atherosclerosis

Nahrendorf

McCarthy

Libby

2012

Circulation Research

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

Cited by 46 publications

References 45 publications

Development of a Magnetic Resonance Imaging Protocol for the Characterization of Atherosclerotic Plaque by Using Vascular Cell Adhesion Molecule-1 and Apoptosis-Targeted Ultrasmall Superparamagnetic Iron Oxide Derivatives

Development of a Magnetic Resonance Imaging Protocol for the Characterization of Atherosclerotic Plaque by Using Vascular Cell Adhesion Molecule-1 and Apoptosis-Targeted Ultrasmall Superparamagnetic Iron Oxide Derivatives

Challenges and Opportunities in Absorption, Distribution, Metabolism, and Excretion Studies of Therapeutic Biologics

Over a Hump for Imaging Atherosclerosis

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