**2. Targeted microbubbles**

Microbubbles used for contrast enhanced and molecular sonography consist of an encapsulated gas covered by a lipid shell. They range from 2 to 5 microns in size, approximately one-third the size of an erythrocyte. As such, they remain intravascular and do not extravasate into the interstitium. They enhance the signal-to-noise ratio due to their oscillations in an insonated field as best depicted using harmonics.

A variety of targeting ligands, such as the vasogenic growth factor (VEGF) receptor, can be attached to the shell of a microbubble using the streptavidin-biotin spacer (**Figure 1**) [2]. Molecular sonography has been used to evaluate tumor angiogenesis, anti-immune encephalomyelitis, inflammatory bowel disease, transplant rejection and abnormal myocardial perfusion. The most frequently utilized application of molecular sonography involves a VEGF receptor antibody can be used as a ligand on a microbubble to detect tumor microvessels (**Figure 2**) [3]. This has shown to provide early detection of several cancers in murine models, notably pancreatic, prostate, and squamous cell carcinoma.

Labeled microbubbles may have an important role in monitoring tumor response to anti-angiogenic medications. In a preclinical proof of concept study using colon cancer models, 3D molecular sonography showed close correlation with treatment response to antiangiogenetic therapy [4].

Microbubble sonography can be used to assess the potential efficacy of specific anti-angiogenetic medications. In a pilot study of patients with refractory hepatocellular carcinomas, we found that a significant decrease in vascularity was seen in responsive vs. non-responsive tumors in the first 15 days after treatment was initiated (**Figure 3**) [5].

Similarly, molecular sonography has been studied as a means to evaluate acute ileitis in a swine model that targeted E- and P-selectin. The intensity of the sonographic signal correlated to the amount of immunofluorescence [6].

*Molecular Sonography: Current and Future Applications DOI: http://dx.doi.org/10.5772/intechopen.99903*

**Figure 2.**

*Molecular sonograms of implanted murine tumor with low (top) and high (bottom) VEGF receptors as confirmed with immunofluorescence [2].*
