Ultrasound Molecular Imaging of Cancer: Design and Formulation Strategies of Targeted Contrast Agents

Gas-filled particles (microbubbles) can be prepared and stabilized for intravascular use as contrast agents in ultrasound imaging. Microbubbles are used in clinics as blood pool contrast materials for the past two decades. Shell of these bubbles is made of biocompatible and biodegradable lipids, proteins, and/or polymers. Gas core is air, or, lately, a perfluorinated gas, poorly soluble in water and blood. Making them useful for molecular targeting and molecular imaging in oncology is accomplished by decorating the shell of these particles with targeting ligands, that will selectively bind to the specific markers of tumor vasculature. In this review we discuss the formulation strategy for microbubble preparation, the logic of bubble shell selection, coupling tools that are used for the attachment of targeting ligands, and examples of the application of gas-filled bubbles for molecular imaging in oncology.