| abstract |
Proteinaceous gas- or gas precursor-containing microbubble contrast agents, e.g. for use in ultrasound and/or MR imaging, in which the protein matrix is crosslinked by reaction with a bifunctional aldehyde (e.g. a dialdehyde such as glutaraldehyde or an α,β-unsaturated aldehyde such as acrolein) in an aqueous medium at substantially neutral pH exhibit improved in vivo and storage stabilities, particularly if the matrix is also reacted with a Schiff's base reducing agent such as a borohydride. Modification of the size distribution of such crosslinked proteinaceous gas-containing contrast agents, e.g. to reduce the mean size of the microbubbles, further enhances their stability and permits preparation of novel contrast agents having a particularly narrow microbubble size distribution. |