VEGFR-targeted ultrasound may improve detection of pancreatic cancer

1. Ultrasound with a vascular endothelial growth factor receptor type 2 (VEGFR2)-targeted contrast agent allowed for noninvasive detection of pancreatic ductal adenocarcinoma (PDAC) in a transgenic mice model.

2. The degree of enhancement with VEGFR2-targeted contrast was significantly higher in PDAC lesions as compared to normal pancreatic tissue.

Evidence Rating Level: 3 (Average)       

Study Rundown: Pancreatic ductal adenocarcinoma is a highly aggressive cancer that is often diagnosed at an advanced stage. Multiple approaches to screening with diagnostic imaging have been previously been attempted with unfavorable results, and new strategies that allow for early detection are needed. Targeted contrast-enhanced ultrasound (US) is an emerging imaging technique that combines standard US technology with molecularly-targeted contrast agents to assess biological processes such as angiogenesis.  Angiogenesis, the growth of new blood vessels, plays a critical role in the development of tumors and metastases, making it an attractive target for both cancer imaging and therapy. VEGFR2 is considered a key molecular marker of tumor angiogenesis and it is overexpressed in several cancers, including PDAC. The goal of the present study was to investigate the utility of VEGFR2-targeted US in PDAC detection. A transgenic mouse model of PDAC was used, and VEGFR2-targeted microbubbles (MB) were employed as an US contrast material. Researchers found that the microbubbles preferentially targeted PDAC cells while sparing normal pancreatic tissue, resulting in significantly higher signal intensities by US in PDAC mice than in control mice. Size was found to be important in PDAC visibility, with smaller tumors appearing more conspicuous than larger tumors. These results represent a major step forward for pancreatic cancer screening, but further studies in humans are needed to definitively support the use of VEGFR2-based imaging among PDAC patients.

Click to read the study in Radiology

Relevant Reading: Tumor angiogenic marker expression levels during tumor growth: longitudinal assessment with molecularly targeted microbubbles and US imaging

In-Depth [animal study]: Forty-four transgenic mice bred for early PDAC development were studied using US after intravenous injection of VEGFR2 -targeted microbubble contrast. Sixty-four wild-type mice with no evidence of PDAC  underwent the same protocol and served as healthy controls. Following contrast-enhanced US, pancreatic tissue was harvested from both PDAC and control mice and analyzed with hematoxylin-eosin staining and immunostaining for VEGFR2 expression. Ultrasound signal intensity was found to be 26.8-fold higher in transgenic mice harboring PDAC lesions than in healthy, wild type mice (P < .001). VEGFR2-mediated signal intensity varied with PDAC lesion size; tumors  less than 3 mm in diameter demonstrated a 30.8-fold higher signal intensity than control tissue (P < .001), while lesions greater than 3 mm in diameter had only 1.7-fold higher signal intensity. Histologic evaluation confirmed significantly higher VEGFR2 expression in pancreatic tumors as compared with healthy, wild-type pancreatic tissue, supporting the specificity of VEGFR2-targeted microbubbles in PDAC lesion identification.

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Image: PD

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