Optison

In addition to the selection of gas for the microbubble core, a wide variety of approaches is available for the construction of the stable microbubble shell. The shells were initially copied directly from the first-generation microbubble design (e.g., Albunex to Optison). Later on, new shells were also developed which helped to improve microbubble circulation time and stability in the bloodstream. 

The materials used for the construction of the microbubble shell have to be fully biocompatible. They are either natural products (human albumin in the denatured albumin shell of Albunex and Optison), synthetic versions of natural... 

Optison/denatured albumin shell CjFg Approved in US [23]... 

Another example of a delivery system based on microbubbles and ultrasound is the delivery of circulating microparticles (polymer latex beads) or fluorescent red blood cells outside of the capillaries into the surrounding tissues by the action of ultrasound on the co-injected Optison microbubbles [79]. Interestingly, polymer beads and red blood cells could be detected tens of micrometers away from the capillaries where the bubble destruction took place. This may imply that during rapid destruction of a microbubble in a very strong ultrasound field, adjacent microsphere beads in the bloodstream can be propelled deep into the surrounding tissues. 

We have experience in using two different ultrasound contrast agents [Optison (GE Healthcare, Milwaukee, WI, USA) and Definity (Bristol-Myers Squibb Medical Imaging, N. Billerica, MA, USA)] that produce almost identical results (18). Both are stored at +4°C. It is likely that similar results could be obtained with other ultrasound contrast agents containing microbubbles. 

These ultrasound contrast agents consist of pie-formed bubbles that are either lipid (Definity ) or human serum albumin (Optison ) shells filled with the perfluoro-carbon gas (Perflutren). 

In 50 patients (mean age 59 years) in an intensive care unit who underwent echocardiography examination with intravenous Optison (dose 0.5-1.5 ml), there were no contrast-related adverse effects (4). Good quality echocardiography was obtained in all cases. 

Ellahham S, Hausnerova E, Gottdiener J. Intravenous Optison (FS069) enhances pulmonary vein flow velocity signals a multicenter study. Clin Cardiol 2000 23(2) 91-5. 

Cohen JL, Cheirif J, Segar DS, Gillam LD, Gottdiener JS, Hausnerova E, Bruns DE. Improved left ventricular endocardial border delineation and opacification with OPTISON (FS069), a new echocardiographic contrast agent. Results of a phase III Multicenter Trial. J Am Coll Cardiol 1998 32(3) 746-52. 

Trade names Definity (DuPont) Optison (Amersham) Indications Echocardiogram imaging Category Radiographic contrast medium Half-life 1.3 minutes... 

Coussios CC, Holland CK, Jakubowska L, Huang SL, MacDonald RC, Nagaraj A, McPherson DD (2004) In vitro characterization of liposomes and Optison by acoustic scattering at 3.5 MHz. Ultrasound Med Biol 30 181-190... 

Fig. 1. Aspect and structure of BLs. PEG-liposomes (a) were sonicated with supercharged perfluoropropane gas. After that, they became to BLs (b). Optison (c) and BLs (d) were observed with microscope using the darklite illuminator (NEPAGENE, Co., Ltd), (e) Transmission electron microscopy (ELM) of BLs. (f) Scheme of structure of BLs...

Most recently, interesting work in a mouse model has been conducted in the laboratories of Dr. Martin J.K. Blomley of Imperial College, Hammersmith Hospital,171 wherein the use of Optison and ultrasound to aid plasmid DNA delivery... 

Levovist). In order to increase their lifetime in blood, the second-generation USCAs (e.g., Echogen, Imagent, SonoVue or Optison) were made out of gas with low water solubility (like perfluorcarbon gases or sulfurhexafluoride) and a surface stabilizer to prevent aggregation. 

Most polymer-stabilized UCAs increase image contrast by upward of 20 dB and provide lOOo/o reflection, especially when driven by frequencies at or near resonance.2 "2 Despite these proven benefits, in October 2003 the FDA in the United States added a black box warning to the labeling to previously approved Definity and General Electric s Optison because... 

Several injectable prolonged release biodegradable microspheres are available as licensed products, e.g. Lupron Depot and Risperdal Consta [18, 19]. The injectable ultrasound contrast agent (Optison ) consists of heat-denaturated albumin microspheres filled with the gas octafluoropropane. In a similar manner sulphur hexafluoride containing microspheres (SonoVue ) are used as injectable contrast agent in echocardiography. 

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