Radiology: Molecularly targeted ultrasound may assess tumor growth

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Contrast-enhanced ultrasound imaging with molecularly targeted microbubbles allowed noninvasive in vivo assessment of a vB3 integrin, endoglin and vascular endothelial growth factor receptor 2 expression levels, which vary during tumor growth in subcutaneous cancer xenografts, based on a mouse model study in the March issue of Radiology. The researchers suggested their results may help define promising imaging targets for both early cancer detection and treatment monitoring.

“Expression levels of different tumor angiogenic markers vary during tumor growth in subcutaneous human breast, ovarian and pancreatic cancer xenografts in mice and change at different tumor stages,” wrote the study authors.

Nirupama Deshpande, PhD, from the Molecular Imaging Program and the radiology department at Stanford University School of Medicine in Stanford, Calif., evaluated the use of molecularly targeted microbubbles (MBs) and ultrasonography in the noninvasive assessment of the level of expression of three angiogenic markers, avB3 integrin, endoglin and vascular endothelial growth factor receptor (VEGFR) 2, on tumor vascular endothelial cells in vivo during tumor growth.

The researchers tested the binding specificity of three types of targeted MBs (MB Integrin, MB Endoglin, MB VEGFR2) in cell culture under flow shear stress conditions. In vivo targeted contrast material-enhanced ultrasonography imaging signal using the three MB types was measured at three tumor stages (small, medium and large) in three subcutaneous cancer xenografts (breast, ovarian and pancreatic cancer) in 54 mice. In vivo ultrasound imaging signal was correlated with ex vivo angiogenic marker expression.

Cell attachment of all three MB types was significantly ( P = 0.016) higher compared with control MBs, and this attachment could be significantly ( P = 0.026) decreased by blocking antibodies, according to the authors. Angiogenic marker-expressing cells bound significantly ( P = 0.003) more targeted MBs than negative control cells, and MB attachment significantly ( P < 0.001) correlated with marker expression levels on cells.

In early stage breast and ovarian cancers, in vivo targeted contrast-enhanced ultrasound demonstrated significantly ( P < 0.04) higher endoglin expression than both a vB3 integrin and VEGFR2 expression, whereas in early stage pancreatic cancer, marker expressions were not significantly different ( P > 0.07). The investigators reported finding a good correlation ( P < 0.05) between in vivo targeted contrast-enhanced ultrasonography imaging signals using the three MB types and ex vivo immunoblotting results regarding expression levels of the three angiogenic markers.

“The results provide further insights into the biology of tumor angiogenesis and may help in defining promising imaging targets for both early cancer detection and treatment monitoring of cancer using targeted contrast-enhanced ultrasonography imaging,” Deshpande and colleagues conducted.

The National Institutes of Health (NIH) funded the research.