Use of Microbubbles as Ultrasound Contrast Agents for Molecular Imaging

Abstract

The field of ultrasound contrast imaging has been literally bursting in the last decade. It becomes clear that ultrasonography which already plays a pivotal role in clinical diagnostics will become essential to health care management with the rise of ultrasound molecular imaging [6]. Technical breakthrough together with enhanced image processing greatly improved spatial resolution and dynamic range of ultrasound imaging. Ultrasound contrast agents (UCA) for medical imaging have been rapidly translated from exploratory research to clinical application [12]. The next generation of targeted contrast agents (TCA) is currently intensively investigated by numerous research groups. They will open a new era where diagnostics is not only based on pathophysiological signs but also on the molecular signature of a disease [2]. TCA are formulations generating signal enhancement, typically gas-filled microbubbles for ultrasound imaging, which are capable of specific binding to a site of interest. This is usually achieved by coupling a targeting ligand onto the surface of the microbubble. Three types of microbubbles are successively used for the different development stages of targeting projects: non-targeted naked microbubbles, streptavidin-bearing microbubbles and ligand-decorated microbubbles (Fig. 2.1). Open image in new window Fig. 2.1. Flowchart of the development of targeted microbubbles. Naked microbubbles are the ideal blank material to test both in vitro and in vivo experimental setups. Avidin-microbubbles are used for ligand density ranging in vitro and in vivo. Finally pre-clinical grade targeted microbubbles produced in large batches by covalent coupling are meant for large-scale in vivo studies in several animal models