Ovarian Cancer Imaging Using Contrast-Enhanced Ultrasound (CEUS)
Charles Drescher, MD - Fred Hutchison Cancer Research Center
Sanjiv (Sam) Gambhir, MD, Ph - Stanford University
The primary objective of this project is to validate and refine molecularly targeted microbubble contrast enhanced ultrasound (CEUS) for non-invasive, in-vivo imaging of the ovarian cancer vascular network. Microbubbles are encapsulated gaseous particles that compress and expand their shape in response to an isonation source and generate strong acoustic signals that exceed conventional US backscatter. Ranging in size from 2 to 6 um, microbubbles persist in the blood stream for several minutes enabling assessment of their presence at the tissue microvascular level. Important to this project is the finding that microbubbles can be targeted to specific antigens on the surface of vascular endothelial cells by attaching ligands to the microbubble shell. Microbubbles functionalized in this way provide detailed information on the vasculature at a molecular level. Dr. Gambhir has successfully used VEGFR2 and αvβ3 targeted microbubbles to sensitively and specifically image cancer associated blood vessels in living mice.
Our translational research goal is to apply this highly promising approach as part of a multi-modal ovarian cancer screening strategy. As a first step toward our goal we will conduct a first ever Phase I clinical trial of CEUS using microbubbles targeting VEGFR2 to image ovarian cancer associated angiogenesis in women. Additionally, we will further refine the approach by identifying and validating novel endothelial cell surface proteins that might be better targets for imaging ovarian cancer associated angiogenesis.
Project 2 Publications
1. Willmann JK, Cheng Z, Davis C, Lutz AM, Schipper ML, Nielsen CH, Gambhir SS. Targeted Microbubbles for Imaging Tumor Angiogenesis: Assessment of Whole-Body Biodistribution with Dynamic MicroPET Imaging in Mice. Radiology. 2008 Oct;249(1):212-9. PMCID: PMC2657857
2. Willmann JK, Lutz AM, Paulmurugan R, Patel MR, Chu P, Rosenberg J, Gambhir SS. Dual-targeted Contrast Agent for Ultrasonic Assessment of Tumor Angiogenesis in Vivo. Radiology. 2008 Sep;248(3):936-44. PMCID: PMC2798094
3. Willmann JK, Paulmurugan R, Chen K, Gheysens O, Rodriguez-Porcel M, Lutz AM, Chen IY, Chen X, Gambhir SS. US imaging of tumor angiogenesis with microbubbles targeted to vascular endothelial growth factor receptor type 2 in mice. Radiology. 2008 Feb;246(2):508-18.
4. Lutz AM, Ray P, Willmann JK, Drescher C, Gambhir SS. 2-Deoxy-2-[F-18]fluoro-D: -glucose Accumulation in Ovarian Carcinoma Cell Lines. Mol Imaging Biol. 2007 Sep-Oct;9(5):260-6.