Ultrasonic imaging of molecular targets.

Today nuclear medicine is the only modality that is clinically successful in molecular imaging. However, other modalities compete with its excellent sensitivity in imaging molecular targets. In the last 10 years ultrasound imaging has shown the potential to provide sufficiently high sensitivity for the molecular imaging of vascular targets. These advances are based on the joint development of microbubble contrast media and the methods to image them with high sensitivity. Ultrasound-contrast-enhanced imaging strategies make use of the specific physical properties of microbubbles such as resonance, nonlinear oscillation, and collapse. The size of microbubbles limits their use to the vascular space. Thus, the main applications of ultrasound for molecular imaging are inflammation, thrombi, and angiogenesis, for which successful contrast enhancement has been achieved in animal models. Main molecular targets used to date include selectins, alpha(v)beta(3) or alpha(5)beta(1) integrins, glycoprotein (GP) IIb/IIIa, intracellular adhesion molecule ICAM-1, and vascular endothelial growth factor receptor VEGFR2. Results from animal studies indicate that ultrasound could play a major role in vascular molecular imaging for diagnosis and treatment monitoring. Additional effects of insonified microbubbles (e.g., opening of the blood-brain barrier or increased transfection efficiency in gene therapy) are attributed to the transient opening of cell membranes known as "sonoporation" and demonstrate further potential for integrated diagnosis and therapy.