Background and Purpose-Molecular imaging of therapeutic interventions with targeted agents that simultaneously carry drugs or genes for local delivery is appealing. We investigated the ability of a novel microbubble carrier (immunobubble) for abciximab, a glycoprotein IIb/IIIa receptor inhibitor, for ultrasonographic molecular imaging of human clots. Methods-Human thrombi were incubated with immunobubbles conjugated with abciximab. Control clots were incubated in either saline or with immunobubbles conjugated with nonspecific antibody. We evaluated immunobubble suspensions with variable concentrations of encapsulated gas and measured mean acoustic intensity of the incubated clots. In vivo molecular imaging of human thrombi with abciximab immunobubbles was evaluated in a rat model of carotid artery occlusion. Results-Mean acoustic intensity was significantly higher for abciximab immunobubbles as compared with control immunobubbles under all conditions tested with maximum difference in intensity at a gas volume of 0.2 L (Pϭ0.0013 for mechanical index 0.05, Pϭ0.0001 for mechanical index 0.7). Binding of abciximab immunobubbles to clots in vitro led to enhanced echogenicity dependent on bubble concentration. In vivo ultrasonic detectability of carotid thrombi was significantly higher for clots targeted with abciximab immunobubbles (PϽ0.05). Quantification of in vivo contrast enhancement displayed a highly significant increment for abciximab immunobubble-targeted clots compared with nonspecific immunobubble-targeted clots (PϽ0.0001) and to native clots (PϽ0.0001). Conclusions-This study demonstrates the feasibility of using a therapeutic agent for selective targeting in vascular imaging. Abciximab immunobubbles improve visualization of human clots both in vitro and in an in vivo model of acute arterial thrombotic occlusion.
This article describes the preparation of macroporous cross-linked poly(dicyclopentadiene) by chemically induced phase separation. Dicyclopentadiene was polymerized and cross-linked by metathesis in the presence of 2-propanol, using a ruthenium-based catalyst, and then dried under vacuum. The resulting porous materials were characterized by SEM, density measurements, and mercury porosimetry. By varying the initial 2-propanol content, it was shown that closed or open cell porosity could be obtained, with narrow pore size distributions and micrometric average access diameters. A linear dependence of the pore volume fraction and the initial 2-propanol content was also observed, suggesting easy tailoring of the former.
Macroporous poly(dicyclopentadiene) beads have been produced via chemically induced phase separation in suspension polymerization. Phase separation is promoted by the enthalpic and entropic changes induced by the polymerization of dicyclopentadiene. By using poly(1,2-butylene glycol) monobutyl ether (M n 500 g/mol), which is not soluble in the suspending medium, as the porogen, the stabilized droplets of the monomer/porogen mixture can be considered microreactors in which both polymerization and phase separation occur, resulting in solid, biphasic microspheres. The porogen is then extracted with methanol and the particles are finally dried. The resulting macroporous crosslinked poly(dicyclopentadiene) beads are analyzed by scanning electron microscopy, mercury intrusion porosimetry, and nitrogen adsorption and are compared with similar bulk samples. Materials containing isolated pores as well as microstructures built with agglomerated particles have been produced. The porous microspheres showed micrometric average pores' access diameters and specific surface areas ranging from 1.3 to 3.1 m 2 /g.
Stroke is one of the major causes of death and disabilities in industrialized countries. Ultrasound imaging is a largely wide spread bedside technique that is easily accessible and valuable in case of emergency but suffers from the fact that the ultrasound wave has to cross the skull for brain imaging. However, ultrasound contrast agents and new contrast-specific imaging modalities have helped to improve the diagnostic quality of transcranial ultrasonography. This review article surveys and discusses the current state of microbubbles technology and the use of contrast-enhanced transcranial ultrasound for the assessment of brain perfusion. Future aspects and expectations in contrast agent functionality, such as targeting and drug or gene delivery, acceleration of thrombolysis, and imaging technology, are also discussed.
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