Molecularly-Targeted Ultrasound in Ovarian Cancer

卵巢癌是所有妇科癌症中最致命的。由于非特定症状 这种疾病经常在病情发展到很严重时才被发现。尽管改进了，而且永远不会 更积极的治疗方法，5年存活率不到50%。早期发现 卵巢癌是提高存活率的关键，但目前确诊的病例不到30% 当早期疾病仍局限于卵巢时。卵巢癌的预后可能是 通过开发一种非侵入性分子成像策略进行了改进，该策略可以可靠地 鉴别卵巢良恶性肿块并发现早期无症状 疾病。超声(US)是目前大多数临床情况下的一线卵巢成像测试， 但具有导致在筛选设置中表现不佳的重要限制。一个 提高美国敏感度和特异度的策略可能有助于将这种方式转变为有用的 卵巢癌早期检测工具。临床前研究表明，超声波 可以通过添加分子靶向微泡造影剂来提高性能 提供卵巢癌相关新生血管的分子信息的试剂。 分子靶向CEUS可能应用于卵巢癌的早期检测以及 卵巢癌抗血管生成治疗的患者选择及疗效监测。 我们的长期目标是将分子靶向CEU方法应用于多个 模式卵巢癌筛查策略，特别是在确定的高危患者群体中。AS 朝着我们的长期目标迈出的重要一步，我们提议进行I/II期临床 VEGFR2靶向CEUS在卵巢癌相关新生血管成像中的应用 对疑似卵巢癌患者和卵巢癌高危患者进行评估 检测限和背景信号。我们将阐明生理性创伤的影响- 愈合相关生理性血管生成的影像表现及最佳成像时间 绝经前患者月经周期中的时点。我们还提议使用 来自临床指示的组织病理学检查的多余组织材料用于探索性研究 进一步验证可能成为未来最佳靶点的新型内皮细胞表面蛋白 卵巢癌相关新生血管的成像。这些新颖的标记可以作为 未来多价微泡的补充目标，有可能进一步 通过处理多个目标提高方法的灵敏度和特异度 同时。

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.