Molecularly-Targeted Ultrasound in Ovarian Cancer

卵巢癌是所有妇科癌症中最致命的。由于非特异性症状 这种疾病通常直到很晚期才被发现。尽管不断改进， 更积极的治疗方法，5年生存率低于50%。早期发现 卵巢癌是提高生存率的关键，但目前只有不到30%的病例被诊断出来， 当早期疾病仍然局限于卵巢时。卵巢癌的结果可能是 通过开发一种非侵入性分子成像策略， 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检查， 但是具有导致在筛选设置中的次优性能的重要限制。一 提高超声敏感性和特异性的策略可能有助于将超声模式转变为有用的 卵巢癌的早期诊断临床前研究表明， 通过添加分子靶向微泡造影剂 提供关于卵巢癌相关的新血管的分子信息的药剂。 分子靶向CEUS可应用于卵巢癌的早期检测， 选择患者并监测卵巢癌对抗血管生成治疗的反应。 我们的长期转化目标是将分子靶向CEUS方法应用于多靶点， 模式卵巢癌筛查策略，特别是在确定的高风险患者人群中。作为 这是朝着我们的长期目标迈出的重要一步，我们建议进行I/II期临床试验， VEGFR2靶向CEUS用于卵巢癌相关新生血管成像的试验 疑似卵巢癌患者和卵巢癌高危患者，以评估 检测限和背景信号。我们将阐明生理创伤的影响- 愈合相关的生理性血管生成对影像学表现和最佳成像时间的影响 绝经前患者月经周期内的时间点。我们还建议使用 用于探索性研究的有临床指征的组织病理学检查的过量组织材料， 进一步验证了新的内皮细胞表面蛋白，这些蛋白可能是未来的最佳靶点， 卵巢癌相关的新血管生成的成像。这些新的标记物可以作为 未来多价微泡的互补靶点， 通过针对多个靶点提高方法的灵敏度和特异性 同步

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.