Binding a tumor endothelial marker with an ultrasound contrast agent offers the promise of greatly improved resolution and tumor detection capabilities.
That's according to a team of researchers from the University of North Carolina (UNC) at Chapel Hill, led by Dr. Nancy Klauber-DeMore and Paul Dayton, PhD.
The UNC group developed a molecular imaging ultrasound contrast agent by binding a microbubble contrast agent with the secreted frizzled related protein 2 (SFRP2) tumor marker, an antibody that has increased expression in many human cancers. Preclinical testing showed that the SFRP2 molecularly targeted contrast agent could specifically visualize tumor vasculature of angiosarcoma lesions, without visualizing normal blood vessels.
"This novel contrast agent could be useful to help differentiate between benign and malignant lesions on ultrasound, increasing the specificity of ultrasound for cancer detection," the authors wrote in an article published online January 29 in PLOS One.
After an earlier discovery by Klauber-DeMore's lab that angiosarcoma cells produce an excess of SFRP2, her group sought to investigate use of the protein for monitoring cancer progression within blood vessels, according to a statement. A SFRP2 polyclonal antibody was used to create the contrast agent, which was delivered intravenously to nude mice that had been injected with angiosarcoma cells.
The researchers acquired ultrasound B-mode images of the mice using an Acuson Sequoia 512 scanner (Siemens Healthcare) at 15 MHz. The group imaged both the targeted agent and a control ultrasound contrast agent.
When compared with the control contrast agent, the SFRP2-targeted contrast agent detected the tumor vasculature with significantly more signal intensity, according to the researchers.
Average pixel intensity increased as tumor volume increased, and correlation analysis found a highly significant relationship (p = 0.003, Pearson r = 0.78) between tumor volume and SFRP2-targeted video signal.
Klauber-DeMore said the next phase of the research will involve determining how well the technique works with other tumor types, as well as studying its effect on breast cancer. In addition, the team will investigate whether it can be used to monitor chemotherapy response, and the researchers will also evaluate whether it can be used to detect and visualize very small tumors.
