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Updated: May 4, 2026
Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence
Published on: November 2, 2014
Ultrasound molecular imaging in a human CD276 expression-modulated murine ovarian cancer model
Amelie M Lutz1, Sunitha V Bachawal, Charles W Drescher
1Authors' Affiliations: Departments of Radiology and Bioengineering and Materials Science and Engineering; Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California; and Division of Public Health Sciences, Fred Hutchinson, Cancer Research Center, Seattle, Washington.
Purpose:
To develop a mouse ovarian cancer model that allows modulating the expression levels of human vascular targets in mouse xenograft tumors and to test whether expression of CD276 during tumor angiogenesis can be visualized by molecularly targeted ultrasound in vivo.
Experimental Design:
CD276-expressing MILE SVEN 1 (MS1) mouse endothelial cells were engineered and used for coinjection with 2008 human ovarian cancer cells for subcutaneous xenograft tumor induction in 15 nude mice. Fourteen control mice were injected with 2008 cells only. After confirming their binding specificity in flow chamber cell attachment studies, anti-CD276 antibody-functionalized contrast microbubbles were used for in vivo CD276-targeted contrast-enhanced ultrasound imaging.
Results:
CD276-targeted ultrasound imaging signal was significantly higher (P = 0.006) in mixed MS1/2008 tumors than in control tumors. Compared with control microbubbles, the ultrasound signal using CD276-targeted microbubbles was significantly higher (P = 0.002), and blocking with purified anti-CD276 antibody significantly decreased (P = 0.0096) the signal in mixed MS1/2008 tumors. Immunofluorescence analysis of the tumor tissue confirmed higher quantitative immunofluorescence signal in mixed MS1/2008 tumors than in control 2008 only tumors, but showed not significantly different (P = 0.54) microvessel density.
Conclusions:
Our novel small animal model allows for modulating the expression of human tumor-associated vascular endothelial imaging targets in a mouse host and these expression differences can be visualized noninvasively by ultrasound molecular imaging. The animal model can be applied to other human vascular targets and may facilitate the preclinical development of new imaging probes such as microbubbles targeted at human vascular markers not expressed in mice.
Insights
This study developed a novel mouse ovarian cancer model to visualize human vascular targets like CD276 using ultrasound molecular imaging. The targeted ultrasound successfully detected CD276 expression in engineered tumors, aiding preclinical imaging probe development.
Area of Science:
- Oncology
- Biomedical Imaging
- Vascular Biology
Background:
- Developing accurate animal models for human cancer research is crucial.
- Targeted molecular imaging offers non-invasive methods to assess tumor characteristics.
- CD276 is a vascular target implicated in tumor angiogenesis.
Purpose of the Study:
- To create a mouse ovarian cancer model with adjustable human vascular target expression.
- To evaluate the in vivo visualization of CD276 during tumor angiogenesis using molecularly targeted ultrasound.
- To assess the utility of this model for preclinical imaging probe development.
Main Methods:
- Engineered CD276-expressing endothelial cells (MS1) for co-injection with human ovarian cancer cells (2008) in a xenograft model.
- Utilized anti-CD276 antibody-functionalized microbubbles for targeted contrast-enhanced ultrasound imaging.
- Performed flow chamber studies for binding specificity and immunofluorescence for validation.
Main Results:
- CD276-targeted ultrasound showed significantly higher signals in tumors with engineered MS1 cells compared to controls (P = 0.006).
- Targeted microbubbles yielded higher signals than control microbubbles (P = 0.002), and signal was reduced by blocking antibody (P = 0.0096).
- Immunofluorescence confirmed higher CD276 expression in engineered tumors, but microvessel density was not significantly different.
Conclusions:
- A novel mouse model enables modulation and non-invasive visualization of human vascular targets in xenograft tumors via ultrasound molecular imaging.
- This model facilitates the preclinical evaluation of imaging probes targeting human vascular markers.
- The approach is adaptable for other vascular targets, advancing diagnostic imaging development.
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