FELLOW:ROJAS, J Novel Ultrasound Molecular Imaging for Assessment of Tumor Response to Therapy

Research project

Description

Renal Cell Carcinoma (RCC) comprises 2% of all cancers, but has a very poor 5-year survival rate. Antiangiogenic therapy has been shown to be an effective therapy, but eventually resistance is developed in most cases and therefore, it is important to evaluate and track treatment efficacy. Different Contrast Enhanced Ultrasonography techniques such as Ultrasound Molecular Imaging (USMI), which allows for the quantification of biomarker expression, has been shown to aid assessment of tumor response to therapy. Phase-Change contrast Agents (PCCAs) have advantages such as increased circulation time over the commonly used microbubble contrast agents, and produce a unique acoustic signature. PCCAs have a liquid core that is not echogenic, but can be vaporized (activated) into highly echogenic microbubbles. Studies have examined the contrast generated by PCCAs, but none have explored their potential as diagnostic agents for USMI.

Our group has developed low-boiling-point PCCAs, which can be used with safer acoustic parameters than conventional PCCAs. Clinical systems are difficult to modify in order to use PCCAs, so we have used a programmable Verasonics ultrasound machine to demonstrate the in-vivo feasibility of using low-boiling-point PCCAs for contrast imaging. Additionally, our group has demonstrated USMI with low-boiling-point PCCAs in-vitro. The central hypothesis of this proposal is that PCCAs can be used for USMI in order to track disease progression and evaluate response to therapy.

In the first aim of this project, I will write scripts to control the Verasonics system to efficiently activate and image the contrast generated by activated PCCAs, and capture the unique signal produced by the activation of the agents. I expect that this aim will produce two imaging techniques that can effectively capture the contrast from low-boiling-point PCCAs, and can detect small changes in biomarker expression.

In the second aim, I will use the two imaging modalities to test the sensitivity and specificity of USMI with low-boiling-point PCCAs for the detection of cancer. I will accomplish this aim by imaging mice with growing RCC tumors and using a blinded reader-study to calculate sensitivity and specificity of detection. I expect that both imaging methods will be highly sensitive and specific to detection of cancer.

For the final aim, I will use the two imaging techniques developed I the first aim to evaluate response to therapy using USMI with low-boiling-point PCCAs by imaging mice with RCC tumors that are being treated with the antiangiogenic drug Sutent. I expect that both methods will be able to track response to therapy accurately, compared to the long term growth curve, which is the gold-standard.
StatusActive
Effective start/end date8/1/157/31/18

Funding

  • NIH National Cancer Institute (NCI)

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Molecular Imaging
Contrast Media
Ultrasonography
Neoplasms
Therapeutics
Renal Cell Carcinoma
Microbubbles
Acoustics
Biomarkers
Sensitivity and Specificity
Gold
Disease Progression