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Perfluoropropane-filled, sorbitan monostearate– and polyoxyethylene 40 stearate–shelled nanobubbles.


Shan L.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2010 Aug 02 [updated 2010 Sep 01].


Perfluoropropane (PFC)-filled, sorbitan monostearate (also known as Span 60 (S60))- and polyoxyethylene 40 stearate (PEG40S)-shelled nanobubbles (NB), abbreviated as PFC-S60-PEG40S-NB, is a non-targeted ultrasound contrast agent developed by Xing et al. for tumor imaging on the basis of enhanced permeability and retention effect of tumor vasculature (1). Microbubble agents are the most common type of ultrasound contrast agents and also the only type of these agents to be approved by the United States Food and Drug Administration (2-4). These microbubbles are filled with air or with a water-insoluble gas such as octafluoropropane (C3F8), decafluorobutane, or sulfur hexafluoride (5). The microbubble shell, designed to prevent gas diffusion, can be made of lipids, denatured albumin, or polymers (5). Although microbubbles are highly echogenic, the efficiency of in vivo contrast enhancement is closely related to the microbubble size, surface charge, shell composition, surface architecture, and gas core, particularly in the context of passive targeting (1, 5, 6). In terms of size, the resonant frequency of a microbubble is directly dependent on its size, and the contrast enhancement is closely associated with the size variance among microbubbles (4, 6). Currently, microbubble-enhanced ultrasound imaging is used to image blood perfusion and to measure blood flow rate in the heart, liver, and other organs (2, 7, 8). The mean size of most microbubble contrast agents is less than or approximately equal to the size of red blood cells, although the shell thickness varies from 10 nm to 200 nm. Microbubbles with a diameter <10 µm exhibit effective flow similar to that of red blood cells in the vascular system. Tumor vasculature is characterized by the presence of open pores (380–780 nm) (9, 10). In contrast to blood-pool microbubbles, nanobubbles can pass more efficiently through the pores and accumulate within tumors. Therefore, a better imaging contrast may be achieved. Xing et al. developed a biocompatible PFC-filled nanobubble contrast agent by ultrasonication of a mixture of S60 and PEG40S, followed by isolation of the nanobubble subpopulation from the parent suspensions (1). S60 formed a condensed monolayer to prevent PFC escape from the core, while PEG40S was incorporated into the nanobubble shell to serve as a steric stabilizer. PEG40S is known to be a biocompatible, degradable, and nontoxic surfactant that is widely used in food products and pharmaceuticals. This chapter describes the data obtained by Xing et al. with PFC-S60-PEG40S-NB (1).

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