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Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery.

Paefgen V, Doleschel D, Kiessling F - Front Pharmacol (2015)

Bottom Line: Bubbles can also be loaded with or attached to drugs, peptides or genes and can be destroyed by US pulses to locally release the entrapped agent.Recent studies show that US CAs are also valuable tools in hyperthermia-induced ablation therapy of tumors, or can increase cellular uptake of locally released drugs by enhancing membrane permeability.Additionally, an overview of the recent developments in US probe design for functional and molecular diagnosis as well as for drug delivery is given.

View Article: PubMed Central - PubMed

Affiliation: Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, Aachen Germany.

ABSTRACT
Ultrasound (US) is one of the most frequently used diagnostic methods. It is a non-invasive, comparably inexpensive imaging method with a broad spectrum of applications, which can be increased even more by using bubbles as contrast agents (CAs). There are various different types of bubbles: filled with different gases, composed of soft- or hard-shell materials, and ranging in size from nano- to micrometers. These intravascular CAs enable functional analyses, e.g., to acquire organ perfusion in real-time. Molecular analyses are achieved by coupling specific ligands to the bubbles' shell, which bind to marker molecules in the area of interest. Bubbles can also be loaded with or attached to drugs, peptides or genes and can be destroyed by US pulses to locally release the entrapped agent. Recent studies show that US CAs are also valuable tools in hyperthermia-induced ablation therapy of tumors, or can increase cellular uptake of locally released drugs by enhancing membrane permeability. This review summarizes important steps in the development of US CAs and introduces the current clinical applications of contrast-enhanced US. Additionally, an overview of the recent developments in US probe design for functional and molecular diagnosis as well as for drug delivery is given.

No MeSH data available.


Related in: MedlinePlus

Active targeting by coupling of ligands to MB that bind to structures overexpressed or exclusively expressed on tumor endothelium (schematic illustration, not drawn to scale).
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Figure 2: Active targeting by coupling of ligands to MB that bind to structures overexpressed or exclusively expressed on tumor endothelium (schematic illustration, not drawn to scale).

Mentions: Active targeting requires specific surface modification. Since MB are limited to the vascular compartment, their targets need to be expressed on the luminal side of endothelial cells in pathological environments (Figure 2). Therefore, the first approaches toward targeted MB aimed for thrombosis diagnostics and investigated the blood clot dissolving properties of US application. Unger et al. (1998, 2000) used for their first in vitro system the shortest functional peptide sequence of fibrinogen, known to bind to glycoprotein IIb/IIIa on platelets, and linked it to a lipid-shell bubble. In a binding assay, they observed both binding and signal enhancement. Their first in vivo studies in a dog model showed similarly promising results (Unger et al., 1998, 2000). Other early approaches involved targeting the intercellular adhesion molecule 1 (ICAM-1) for the detection of atherogenesis. Villanueva et al. (1998) used an anti-ICAM-1 antibody covalently bound to a lipid-shell bubble, showing a 40-times higher adhesion of labeled bubbles to interleukin-1β-activated ICAM-1 overexpressing endothelial cells in an in vitro flow system, compared to untreated endothelial cells. For a first in vivo approach, a rat model of heterotopic heart transplant rejection was chosen. Both successful binding and a strong US contrast enhancement were demonstrated in the transplanted organ undergoing acute rejection (Weller et al., 2003).


Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery.

Paefgen V, Doleschel D, Kiessling F - Front Pharmacol (2015)

Active targeting by coupling of ligands to MB that bind to structures overexpressed or exclusively expressed on tumor endothelium (schematic illustration, not drawn to scale).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4584939&req=5

Figure 2: Active targeting by coupling of ligands to MB that bind to structures overexpressed or exclusively expressed on tumor endothelium (schematic illustration, not drawn to scale).
Mentions: Active targeting requires specific surface modification. Since MB are limited to the vascular compartment, their targets need to be expressed on the luminal side of endothelial cells in pathological environments (Figure 2). Therefore, the first approaches toward targeted MB aimed for thrombosis diagnostics and investigated the blood clot dissolving properties of US application. Unger et al. (1998, 2000) used for their first in vitro system the shortest functional peptide sequence of fibrinogen, known to bind to glycoprotein IIb/IIIa on platelets, and linked it to a lipid-shell bubble. In a binding assay, they observed both binding and signal enhancement. Their first in vivo studies in a dog model showed similarly promising results (Unger et al., 1998, 2000). Other early approaches involved targeting the intercellular adhesion molecule 1 (ICAM-1) for the detection of atherogenesis. Villanueva et al. (1998) used an anti-ICAM-1 antibody covalently bound to a lipid-shell bubble, showing a 40-times higher adhesion of labeled bubbles to interleukin-1β-activated ICAM-1 overexpressing endothelial cells in an in vitro flow system, compared to untreated endothelial cells. For a first in vivo approach, a rat model of heterotopic heart transplant rejection was chosen. Both successful binding and a strong US contrast enhancement were demonstrated in the transplanted organ undergoing acute rejection (Weller et al., 2003).

Bottom Line: Bubbles can also be loaded with or attached to drugs, peptides or genes and can be destroyed by US pulses to locally release the entrapped agent.Recent studies show that US CAs are also valuable tools in hyperthermia-induced ablation therapy of tumors, or can increase cellular uptake of locally released drugs by enhancing membrane permeability.Additionally, an overview of the recent developments in US probe design for functional and molecular diagnosis as well as for drug delivery is given.

View Article: PubMed Central - PubMed

Affiliation: Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, Aachen Germany.

ABSTRACT
Ultrasound (US) is one of the most frequently used diagnostic methods. It is a non-invasive, comparably inexpensive imaging method with a broad spectrum of applications, which can be increased even more by using bubbles as contrast agents (CAs). There are various different types of bubbles: filled with different gases, composed of soft- or hard-shell materials, and ranging in size from nano- to micrometers. These intravascular CAs enable functional analyses, e.g., to acquire organ perfusion in real-time. Molecular analyses are achieved by coupling specific ligands to the bubbles' shell, which bind to marker molecules in the area of interest. Bubbles can also be loaded with or attached to drugs, peptides or genes and can be destroyed by US pulses to locally release the entrapped agent. Recent studies show that US CAs are also valuable tools in hyperthermia-induced ablation therapy of tumors, or can increase cellular uptake of locally released drugs by enhancing membrane permeability. This review summarizes important steps in the development of US CAs and introduces the current clinical applications of contrast-enhanced US. Additionally, an overview of the recent developments in US probe design for functional and molecular diagnosis as well as for drug delivery is given.

No MeSH data available.


Related in: MedlinePlus