MR imaging of thrombi using EP-2104R, a fibrin-specific contrast agent: initial results in patients

Spuentrup, Elmar; Botnar, René M.; Wiethoff, Andrea J.; Ibrahim, Tareq; Kelle, Sebastian; Katoh, Marcus; Özgün, Murat; Nagel, Eike; Vymazal, Josef; Graham, Phil B.; Günther, Rolf W.; Maintz, David

doi:10.1007/s00330-008-0965-2

Cited by 172 publications

(131 citation statements)

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“…Transmetallation competition experiments demonstrated that EP-2104R was highly inert toward gadolinium loss, which is an important property for patient safety. Remarkably, EP-2104R is the first MRI molecular imaging agent to advance to human trials (Spuentrup et al 2008).…”

Section: Molecular Imaging Agents Obtained Using Purified Targetsmentioning

confidence: 99%

Phage display and molecular imaging: expanding fields of vision in living subjects

Cochran

2010

Biotechnology and Genetic Engineering Reviews

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In vivo molecular imaging enables non-invasive visualization of biological processes within living subjects, and holds great promise for diagnosis and monitoring of disease. The ability to create new agents that bind to molecular targets and deliver imaging probes to desired locations in the body is critically important to further advance this field. To address this need, phage display, an established technology for the discovery and development of novel binding agents, is increasingly becoming a key component of many molecular imaging research programs. This review discusses the expanding role played by phage display in the field of molecular imaging with a focus on in vivo applications. Furthermore, new methodological advances in phage display that can be directly applied to the discovery and development of molecular imaging agents are described. Various phage library selection strategies are summarized and compared, including selections against purified target, intact cells, and ex vivo tissue, plus in vivo homing strategies. An outline of the process for converting polypeptides obtained from phage display library selections into successful in vivo imaging agents is provided, including strategies to optimize in vivo performance. Additionally, the use To whom correspondence may be addressed (cochran1@stanford.edu) Abbreviations: scFv, single chain variable fragment; Fab, fragment antigen binding; ELISA, Enzyme-Linked Immunosorbent Assay; NEB, New England Biolabs; PET, positron emission tomography; SPECT, single photon emission computed tomography; NIR, near infrared; PEG, polyethylene glycol; SPARC, secreted protein acidic and rich in cysteine; VCAM-1, vascular cell adhesion molecule; MRI, magnetic resonance imaging; DOTA, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; IC 50 , half maximal inhibitory concentration; CT, computed tomography; K D , equilibrium dissociation constant; EGFR, epidermal growth factor receptor; EGFR-ECD, EGFR extracellular domain; Aβ 42 , amyloid-beta; MMP, matrix metalloprotease; uPAR, urokinase-type plasminogen activator receptor; VEGF, vascular endothelial growth factor; IL-11, Interleukin-11; IL-11αR, Interleukin-11 α-receptor. 58F.V. CoChran and J.r. CoChran of phage particles as imaging agents is also described. In the latter part of the review, a survey of phage-derived in vivo imaging agents is presented, and important recent examples are highlighted. Other imaging applications are also discussed, such as the development of peptide tags for site-specific protein labeling and the use of phage as delivery agents for reporter genes. The review concludes with a discussion of how phage display technology will continue to impact both basic science and clinical applications in the field of molecular imaging.

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Section: Molecular Imaging Agents Obtained Using Purified Targetsmentioning

confidence: 99%

Phage display and molecular imaging: expanding fields of vision in living subjects

Cochran

2010

Biotechnology and Genetic Engineering Reviews

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“…More recent advances have led to the development of targeted contrast agents, aimed at cell surface receptors or proteins. Fibrin and elastin represent an essential component of atherosclerotic plaques, play a key role during their development and progression, and have already been established as promising targets 35, 36, 37. With targeted molecular probes, contrast‐enhanced CMR can visualize and quantify proteins and cells of the atherosclerotic vessel wall, which, given clinical translation is successful, may improve assessment of vulnerable plaques and allow for better‐tailored invasive and non‐invasive therapies ( Figure 1 ).…”

Section: Factsmentioning

confidence: 99%

Magnetic resonance imaging in heart failure, including coronary imaging: numbers, facts, and challenges

et al. 2017

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Coronary artery disease (CAD) is a major risk factor for the incidence and progression of heart failure (HF). HF is characterized by a substantial morbidity and mortality and its lifetime risk is estimated at approximately 20% for men and women. As patients are in most cases identified only after developing overt clinical symptoms, detecting early stages of CAD and HF is of paramount importance. Due to its non‐invasiveness, excellent soft‐tissue contrast, high spatial resolution, and multiparametric nature, cardiovascular magnetic resonance (CMR) imaging has emerged as a promising radiation‐free technique to assess a wide range of cardiovascular diseases such as CAD or HF, enabling a comprehensive evaluation of myocardial anatomy, regional and global function, and viability with the additional benefit of in vivo tissue characterization. CMR has the potential to enhance our understanding of coronary atherosclerosis and the aetiology of HF on functional and biological levels, to identify patients at risk for CAD or HF, and to enable individualized patient management and improved outcomes. Even though larger‐scale studies on the different applications of CMR for the assessment of heart failure are scarce, recent research highlighted new possible clinical applications for CMR in the evaluation of CAD and HF.

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“…The applied dose of 4 -7.5 μmol/kg was significantly lower than the typical non-specific gadolinium-based MR contrast agent dose of 0.1 -0.2 mmol/kg. Finally, this molecular probe was successfully used for detecting thrombi in the aorta, carotid and coronary arteries in a patient; this dem-onstrated that clinical translation of targeted gadoliniumbased molecular MR contrast agents is possible [52]. Larger nanoparticles with more than 50, 000 gadolinium atoms per particle have likewise been successfully employed for in vivo imaging of a jugular thrombus in animals; however, this has not been translated to human application [36].…”

Section: Targeted Molecular Probes For Displaying Plaque Componentsmentioning

confidence: 99%

Molecular Imaging in Cardiovascular Diseases

Botnar

Ebersberger

Noerenberg

et al. 2015

Fortschr Röntgenstr

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Cardiovascular diseases remain the leading cause of morbidity and mortality in industrialized and developing countries. In clinical practice, the in-vivo identification of atherosclerotic lesions, which can lead to complications such as heart attack or stroke, remains difficult. Imaging techniques provide the reference standard for the detection of clinically significant atherosclerotic changes in the coronary and carotid arteries. The assessment of the luminal narrowing is feasible, while the differentiation of stable and potentially unstable or vulnerable atherosclerotic plaques is currently not possible using non-invasive imaging. With high spatial resolution and high soft tissue contrast, magnetic resonance imaging (MRI) is a suitable method for the evaluation of the thin arterial wall. In clinical practice, native MRI of the vessel wall already allows the differentiation and characterization of components of atherosclerotic plaques in the carotid arteries and the aorta. Additional diagnostic information can be gained by the use of non-specific MRI contrast agents. With the development of targeted molecular probes, that highlight specific molecules or cells, pathological processes can be visualized at a molecular level with high spatial resolution. In this review article, the development of pathophysiological changes leading to the development of the arterial wall are introduced and discussed. Additionally, principles of contrast enhanced imaging with non-specific contrast agents and molecular probes will be discussed and latest developments in the field of molecular imaging of the vascular wall will be introduced. Key Points: ??Molecular magnetic resonance imaging has great potential to improve the in vivo characterization of atherosclerotic plaques. ??Based on the molecular information is feasible to enable a better differentiation of stable and unstable (vulnerable) atherosclerotic plaques. Citation Format: ??Botnar RM, Ebersberger H, Noerenberg D et?al. Molecular imaging in cardiovascular diseases. Fortschr R?ntgenstr 2015; 187: 92???101

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MR imaging of thrombi using EP-2104R, a fibrin-specific contrast agent: initial results in patients

Cited by 172 publications

References 64 publications

Phage display and molecular imaging: expanding fields of vision in living subjects

Phage display and molecular imaging: expanding fields of vision in living subjects

Magnetic resonance imaging in heart failure, including coronary imaging: numbers, facts, and challenges

Molecular Imaging in Cardiovascular Diseases

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