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. Lutz AM, Bachawal SV, Drescher CW, Pysz MA, Willmann JK, Gambhir S. Ultrasound Molecular Imaging in a Human CD276 Expression-Modulated Murine Ovarian Cancer Model. Clin Cancer Res. 2014 Mar 1;20(5):1313-22. doi: 10.1158/1078-0432.CCR-13-1642. Epub 2014 Jan 3. PMID:24389327 PubMed Link ↗
2. Drescher CW, Hawley S, Thorpe JD, Marticke S, McIntosh MW, Gambhir SS, Urban N. Impact of screening test performance and cost on mortality reduction and cost-effectiveness of multimodal ovarian cancer screening. Cancer Prev Res (Phila). 2012 Aug;5(8):1015-24. PMCID: PMC3729263. PubMed Link ↗
3. Salzman J, Marinelli RJ, Wang PL, Green AE, Nielsen JS, Nelson BH, Drescher CW, Brown PO. ESRRA-C11orf20 Is a Recurrent Gene Fusion in Serous Ovarian Carcinoma. PLoS Biology. 2011 Sep;9(9):e1001156. PMCID: PMC3176749. PubMed Link ↗
4. Lutz AM, Willmann JK, Drescher CW, Ray P, Cochran FV, Urban N, Gambhir SS. Early Diagnosis of Ovarian Carcinoma: Is a Solution in Sight? Radiology. 2011 May;259(2):329-45. PubMed Link ↗