Chemistry Reference
In-Depth Information
table 14.1
Various types of Microbubbles for ultrasound (us) Imaging.
Microbubble
Shell
Filling Gas
Albunex
®
Human albumin
Air
bR14
Phospholipid
Perfluorobutane
Definity
®
Phospholipid
octafluoropropane
Echogen
®
-
Dodecafluoropentane
Echovist
®
Galactose
Air
Imagent
®
Phospholipid
Perfluorohexane
Myomap
®
Recombinant albumin
Air
optison
®
Human albumin
octafluoropropane
Quantison
®
Recombinant albumin
Air
Perflubron
®
-
Perfluorooctyl bromide
Sonavist
®
Polymer
Air
Sonazoid
®
Phospholipid
Perfluorobutane
SonoVue
®
Phospholipid
Sulphur hexafluoride
usually composed of high molecular weight gas and with a stable lipid or polymer shell. Transpulmonary microbubbles offer
higher diagnostic potential compared to those that cannot pass the pulmonary capillary bed after intravenous injection. A
comparison between different types of microbubbles is shown in Table 14.1 with their coating materials and core gas types.
14.2.1
air-filled Microbubbles
Air-filled microbubbles were the earliest commercially available US contrast agent. While air presents high solubility in
blood, the plasma half-life of air-filled microbubbles is very limited. The air quickly leaks from the microbubble shell into
peripheral blood. In addition, microbubbles that were transpulmonary did not persist long enough for imaging because the
filling air quickly dissolved into the blood.
14.2.1.1 Air-Filled Microbubbles with a Galactose Shell
Echovist® (Schering AG, berlin, Germany) is an air-filled micro-
bubble stabilised with a galactose matrix. Its mean diameter is about 2 μm with 97% smaller than 6 μm; however, Echovist is
not stable enough to pass the lung. They are administered intravenously for echocardiography to opacify right heart cavities and
to detect cardiac shunts [16]. levovist® (Schering AG, berlin, Germany) is another air-filled microbubble with a galactose shell
for imaging to enhance echostructures of liver, kidney, and heart. With the addition of palmitic acid, its stability increases such
that it can pass the lung capillary and give systemic enhancements for up to 5 min. post-injection [17]. After plasma clearance,
levovist can accumulate in the reticuloendothelial system for up to 20 min. for hepatosplenic-specific enhancement [18].
14.2.1.2 Air-Filled Microbubbles with an Albumin Shell
Albunex® (Molecular biosystems Inc., San Diego, CA) is the
first transpulmonary microbubble. It consists of air-filled microbubbles coated with human albumin of 30 to 50 nm thick.
The mean diameter is 3.8 μm with standard deviation of 2.5 μm. Albunex can reach the left ventricle despite its relatively
short half-life of less than 1 min. Quantison® (Quadrant Healthcare, Nottingham, United Kingdom) is similar to Albunex,
but with a relatively thick and rigid shell of recombinant albumin of 200-300 nm. In a biodistribution study of Quantison,
the highest uptake was observed in liver (41.8 ± 10.4%) at 1 h following intravenous administration [19], enabling liver-
specific imaging. Myomap® (Quadrant Healthcare, Nottingham, United Kingdom) is another air-filled microbubble stabi-
lised with recombinant albumin, which is 600-1000 nm thick.
14.2.1.3 Air-Filled Microbubbles with a Cyanoacrylate Shell
Sonavist® (Schering AG, berlin, Germany) is an air-
filled microbubble synthesised by emulsion polymerisation. The shell material is a biodegradable n-butyl-2-cyanoacrylate
polymer. Sonavist can stay intact in the circulation for up to 10 min. post-injection and provides passive targeting for the
reticuloendothelial system [20, 21].
14.2.2
Perfluorocarbon-filled Microbubbles
A significant improvement in the
in vivo
stability of microbubbles was achieved when perfluorocarbon gas began to be used
as the core gas. Perfluorocarbon gases have high molecular weight, low solubility, and low diffusivity, thus they are good
candidates for core gas that can keep the microbubble size stable
in vivo
[22].
