Early detection of ovarian cancer by serum marker and targeted ultrasound imaging

通过血清标志物和靶向超声成像早期检测卵巢癌

• 批准号: 9194808
• 负责人: Animesh Barua
• 金额: $ 36.99万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9194808
• 关键词: 4 year old; Animal Model; Antibodies; Archives; CA-125 Antigen; Cancer Histology; Clinic; Collagen; Contrast Media; Data; Development; Diagnostic; Doppler Ultrasound; Early Diagnosis; Epithelium; Equipment; Evaluation; Event; Follicle Stimulating Hormone Receptor; Gene Expression; Genitourinary system; Glucose; Goals; Gray unit of radiation dose; Health Care Costs; Histology; Human; Image; Immunohistochemistry; Integrins; Longitudinal Studies; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of ovary; Mechanics; Microbubbles; Modeling; Morbidity - disease rate; Nuclear; Nuclear Matrix-Associated Proteins; Operative Surgical Procedures; Ovarian; Ovary; Patients; Physicians; Predictive Value; Prevalence; Process; Proteomics; Reporting; Research; Resolution; Scanning; Screening for Ovarian Cancer; Sensitivity and Specificity; Serum; Serum Markers; Serum Proteins; Signal Transduction; Specificity; Staging; Surface; Survival Rate; Testing; Time; Tissues; Translating; Transvaginal Ultrasound; Ultrasonography; Variant; Woman; early detection biomarkers; egg; genetic regulatory protein; glucose-regulated proteins; imaging agent; imaging biomarker; imaging modality; imaging probe; improved; in vivo; intravenous injection; mesothelin; molecular imaging; mortality; neoplastic cell; novel; ovarian neoplasm; prophylactic; success; targeted agent; targeted imaging; tumor

ABSTRACT We propose to test the validity and specificity of our targeted ultrasound imaging probes in detecting early stage ovarian cancer (OVCA) by transvaginal ultrasound imaging (TVUS). We then test the predictive validity of these probes in a longitudinal study using the laying hen – the only widely available animal model of spontaneous OVCA. OVCA is a fatal gynecological malignancy of women. An effective early detection test could reduce high mortality rate due to OVCA and morbidity associated with exploratory surgeries significantly. Serum levels of CA-125, traditional TVUS and their combination failed to improve early detection of OVCA. CA-125 is non-specific and there is no imaging target in the ovary corresponding to elevated serum CA-125 levels. A fresh approach is needed. An efficient targeted imaging strategy requires appropriate targets and suitable imaging modalities/platforms. Our imaging agents, for the first time, will detect the ovarian tumor and tumor associated neo-angiogenic (TAN) microvessels. Ultrasound is currently used for evaluation of genitourinary masses, and introduction of molecular imaging agents for early OVCA detection would enable physicians to use existing TVUS equipment. We developed TVUS imaging probes targeting follicle stimulating hormone receptor (FSHR) expressing ovarian TAN microvessels and glucose regulatory protein 78 (GRP78)- expressing ovarian tumor epithelium. We tested these probes in laying hens. Our preliminary data supports the validity and specificity of these probes for detecting early OVCA using TVUS in association with serum markers providing proof-of-principle. Thus, in Aim 1 we are proposing to develop novel targeted ultrasound imaging agents including FSHR- and GRP78-targeted imaging probes. Aim 2 will establish the targeted imaging intensities for the detection of early stage OVCA. Aim 3 will test the ability of these probes to detect early stage OVCA and establish the false positive rate in the hen model. Because of the difficulty of identifying patients at early stage OVCA and accessing their tissues, we will use the laying hen to accomplish our research goals. Since the team includes clinicians, our intent is to develop these probes for human use, which could be immediately translated into the clinic.

抽象的 我们建议测试我们的靶向超声成像探头在早期检测中的有效性和特异性 通过经阴道超声成像 (TVUS) 分期卵巢癌 (OVCA)。然后我们测试预测有效性 使用蛋鸡（唯一广泛使用的动物模型）进行的纵向研究中对这些探针进行了研究 自发性OVCA。 OVCA 是女性致命的妇科恶性肿瘤。有效的早期检测测试 可以显着降低 OVCA 导致的高死亡率以及与探查手术相关的发病率。 CA-125、传统 TVUS 及其组合的血清水平未能改善 OVCA 的早期检测。 CA-125 是非特异性的，卵巢中没有与血清 CA-125 升高相对应的成像靶点 水平。需要一种新的方法。有效的靶向成像策略需要适当的目标和 合适的成像方式/平台。我们的显像剂将首次检测卵巢肿瘤并 肿瘤相关的新生血管生成（TAN）微血管。超声波目前用于评估 泌尿生殖系统肿块，以及引入用于早期 OVCA 检测的分子成像剂将使 医生使用现有的 TVUS 设备。我们开发了针对卵泡刺激的 TVUS 成像探头 表达卵巢 TAN 微血管和葡萄糖调节蛋白 78 (GRP78) 的激素受体 (FSHR) - 表达卵巢肿瘤上皮。我们在蛋鸡身上测试了这些探针。我们的初步数据支持 这些探针使用 TVUS 与血清标志物联合检测早期 OVCA 的有效性和特异性 提供原理证明。因此，在目标 1 中，我们建议开发新型靶向超声成像 试剂包括 FSHR 和 GRP78 靶向成像探针。目标 2 将建立目标成像 用于检测早期 OVCA 的强度。目标 3 将测试这些探针检测早期阶段的能力 OVCA 并建立母鸡模型中的假阳性率。由于识别患者的困难 早期 OVCA 并获取其组织，我们将使用蛋鸡来实现我们的研究目标。 由于该团队包括临床医生，我们的目的是开发这些供人类使用的探针，这可能是 立即转化为诊所。