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Targeted Microbubble Contrast-Enhanced Ultrasound Imaging of the Ovarian Cancer V

卵巢癌的靶向微泡超声造影 V

基本信息

批准号：
8322536
负责人：
CHARLES DRESCHER
金额：
$ 25.76万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8322536
关键词：
Abdomen Acoustics Animal Model Animals Antibodies Antibody Affinity Antigen Targeting Antigens Asia Benign Binding Blood Blood Vessels Canada Cancer Model Cell Culture Techniques Cell Surface Proteins Cells Clinic Clinical Contrast Media Data Data Set Detection Development Diagnosis Diagnostic Imaging Disease Dose Early Diagnosis Echocardiography Encapsulated Endothelial Cells Enrollment Europe Goals Human Image Instruction Integrins Lesion Lesion by Morphology Life Ligands Malignant - descriptor Malignant Neoplasms Malignant neoplasm of ovary Maps Microbubbles Microbubbles Ultrasound Contrast Medium Modeling Molecular Molecular Profiling Monitor Mus Natural regeneration Normal tissue morphology Operative Surgical Procedures Outcome Ovarian Ovary Patients Pattern Pelvic Inflammatory Disease Pelvis Peptides Perfusion Pharmacology and Toxicology Phase Phase I Clinical Trials Physiologic Neovascularization Play Postmenopause Premenopause Process Proteins Proteome Proteomics Relative (related person)Risk Reduction Role Safety Salpingo-Oophorectomy Screening for Ovarian Cancer Serous Shapes Signal Transduction Site Source Specificity Staging Stream Streptavidin Surface Testing Time Tissues Translating Translational Research Tumor Angiogenesis Ultrasonography VEGFA gene Vascular Endothelial Cell Vascular Endothelial Growth Factor Receptor-2 Western Blotting Woman Work Xenograft procedure angiogenesis anticancer research cancer diagnosis cancer surgery clinical application corpus luteum density disease diagnosis genome-wide immunogenicity improved in vivo liver imaging molecular phenotype mouse model next generation novel novel marker ovarian neoplasm particle response subcutaneous success transcriptomics tumor volunteer

项目摘要

Microbubbles are encapsulated gaseous particles that compress and expand their shape in response to an insonation source and generate strong acoustic signals that exceed conventional ultrasound 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. Microbubbles have found their way into clinical application as ultrasound contrast agents - e.g. for imaging of liver lesions or echocardiography. Important to this proposal 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. Microbbubles functionalized in this way provide detailed information on the vasculature at a molecular level. Angiogenesis, the recruitment of new blood vessels, occurs at a very early stage in ovarian cancer development and activation ofthe VEGFA/EGFR2 axis plays a crucial role in the process. Our preliminary data demonstrates that VEGFR2 is up-regulated in tumor vessels from ovarian cancer including occult cancer identified at the time of risk-reduction salpingo-oophorectomy. In small animal tumor models we validated non-invasive tumor angiogenesis imaging using contrast enhanced ultrasound (CEUS) with VEGFR2- and/or OvPs-targeted microbubbles and demonstrated that these microbubbles have a high specificity for binding to VEGFR2- and OvPs-expressing cells, respectively, in cell culture and living mice. We also show that ultrasound signal amplification is possible using dual-targeted microbubbles. In Aim 1 of this proposal we will translate our findings from small animal models to the clinic by conducting the first ever Phase 1 clinical trial of VEGFR2 targeted microbubble CEUS to image the ovarian cancer vascular network. Because the molecular phenotype of vascular endothelial cells varies by tissue site and activation state selecting the best antigens for targeting is a critical step in optimizing the approach. In Aim 2 we wilt identify and validate novel endothelial cell surface proteins that may be better markers than or complementary to VEGR2 and validate these markers as in-vivo angiogenesis imaging targets in mouse models. RELEVANCE (See Instructions): The primary objective of this proposal is to validate and refine molecularly targeted microbubble contrast enhanced ultrasound (CEUS) for non-invasive, in-vivo imaging ofthe ovarian cancer vascular network. The approach has the potential to improve outcomes for all women with ovarian cancer through early detection and diagnosis ofthe disease and selecting and monitoring the response of ovarian cancer to anti-angiogenic therapy.

微泡是一种被封装的气体粒子，它们在空气的作用下压缩和膨胀自己的形状