Molecularly-Targeted Ultrasound in Ovarian Cancer

卵巢癌的分子靶向超声

• 批准号: 9217254
• 负责人: Amelie Lutz
• 金额: $ 48.41万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9217254
• 关键词: Address; Anatomy; Animal Cancer Model; Benign; Blood Vessels; CD276 gene; Cancer Patient; Cancerous; Carcinoma; Cell Surface Proteins; Clinical; Clinical Trials; Complement; Contrast Media; Data; Detection; Development; Diagnosis; Diagnostic; Disease; Early Diagnosis; Endothelial Cells; FOLH1 gene; Future; Goals; Gold; Grant; Histology; Histopathology; Human; Image; Imaging Device; Immunohistochemistry; Lesion; Malignant - descriptor; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Malignant neoplasm of prostate; Mammalian Oviducts; Measurable; Menstrual cycle; Methods; Microbubbles; Modality; Molecular; Molecular Target; Outcome; Ovarian; Ovarian Mass; Ovarian Tissue; Ovary; Ovulation; Pathology; Patient Monitoring; Patient risk; Patients; Performance; Phase; Phase I/II Trial; Physiologic Neovascularization; Physiological; Pilot Projects; Premenopause; Risk; Safety; Salpingo-Oophorectomy; Screening for Ovarian Cancer; Sensitivity and Specificity; Signal Transduction; Site; Slide; Specificity; Specimen; Symptoms; Testing; Time; Tissues; Ultrasonography; Vascular Endothelial Cell; Vascular Endothelial Growth Factors; Wound Healing; aggressive therapy; angiogenesis; cancer surgery; clinical material; clinically significant; cohort; contrast enhanced; corpus luteum; diagnostic accuracy; experience; high risk; improved; in vivo imaging; malignant breast neoplasm; molecular imaging; neovasculature; new technology; novel; novel marker; overexpression; patient population; preclinical study; proliferative phase Menstrual cycle; protein biomarkers; receptor; response; screening; targeted imaging; tool; tumor

Ovarian cancer is the most lethal of all the gynecologic cancers. Due to non-specific symptoms the disease frequently remains undetected until well advanced. Despite improved and ever more aggressive therapy approaches, 5-year survival is less than 50%. Early detection of ovarian cancer is critical to improve survival, but currently less than 30% of cases are diagnosed when early stage disease is still confined to the ovary. Ovarian cancer outcomes could be improved by the development of a non-invasive molecular imaging strategy that can reliably distinguish malignant from benign ovarian masses and detect early stage asymptomatic disease. Ultrasound (US) is the current first line ovarian imaging test in most clinical situations, but has important limitations leading to suboptimal performance in the screening setting. A strategy to improve sensitivity and specificity of US may help change the modality into a useful tool for early detection of ovarian cancer. Pre-clinical studies demonstrate that ultrasound performance can be improved by the addition of molecularly targeted microbubble contrast agents that provide molecular information on the ovarian cancer associated neo-vasculature. Molecularly targeted CEUS may be applied to ovarian cancer early detection as well as selecting patients for and monitoring the response of ovarian cancer to anti-angiogenic therapy. Our long-term translational goal is to apply the molecularly targeted CEUS approach in a multi- modal ovarian cancer screening strategy, especially in defined high-risk patient populations. As an important step towards our long-term goal we are proposing to conduct a Phase I/II clinical trial of VEGFR2-targeted CEUS for ovarian cancer-associated neo-angiogenesis imaging in patients with suspected ovarian cancer and in patients at high risk for ovarian cancer to assess the detection limits and background signal. We will elucidate the influence of physiologic wound- healing associated physiologic angiogenesis on imaging findings and the optimal imaging time point within the menstrual cycle in premenopausal patients. We are also proposing to use excess tissue material from clinically indicated histopathology work-up for exploratory studies to further validate novel endothelial cell surface proteins that may be optimal future targets for the imaging of ovarian cancer-associated neo-angiogenesis. These novel markers could serve as complementary targets for future multivalent microbubbles that have the potential to further increase the sensitivity and specificity of the method by addressing multiple targets simultaneously.

卵巢癌是所有妇科癌症中最致命的。由于非特异性症状 该疾病经常一直未被发现，直到良好进展为止。尽管有所改善 更具侵略性的治疗方法，5年生存率小于50％。早期检测 卵巢癌对于提高生存至关重要，但目前不到30％被诊断出 当早期疾病仍然局限于卵巢时。卵巢癌的结果可能是 通过开发非侵入性分子成像策略的改进，可以可靠地 区分恶性剂与良性卵巢肿块并检测早期无症状 疾病。超声（美国）是当前的第一行卵巢成像测试，在大多数临床情况下， 但具有重要的局限性，导致筛选设置中的次优性能。一个 提高我们敏感性和特异性的策略可能有助于将方式改变为有用 早期发现卵巢癌的工具。临床前研究表明超声 通过添加分子靶向微泡对比可以提高性能 提供有关卵巢癌相关的新脉管系统的分子信息的药物。 分子靶向CEU可以应用于卵巢癌的早期检测以及 选择患者并监测卵巢癌对抗血管生成疗法的反应。 我们的长期翻译目标是将分子靶向的CEU方法应用于多个 模态卵巢癌筛查策略，尤其是在定义的高风险患者人群中。作为 朝着长期目标迈出的重要一步，我们提议进行I/II期临床 卵巢癌相关的新血管生成成像的VEGFR2靶向CEU试验 怀疑卵巢癌和患有卵巢癌高风险的患者评估患者 检测极限和背景信号。我们将阐明生理伤口的影响 愈合相关的生理血管生成对成像发现和最佳成像时间 绝经前患者的月经周期内。我们还建议使用 临床上指示的组织病理学的过量组织材料进行探索性研究 进一步验证新型内皮细胞表面蛋白，这可能是最佳的未来目标 卵巢癌相关的新血管生成的成像。这些新颖的标记可以用作 未来多价微泡的互补目标，有可能进一步 通过解决多个目标来提高方法的敏感性和特异性 同时地。