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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

基本信息

批准号：
9751819
负责人：
Animesh Barua
金额：
$ 34.56万
依托单位：
RUSH UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9751819
关键词：
4 year old Animal Model Antibodies Archives CA-125 Antigen Cancer Histology Clinic Collagen Contrast Media Data Development Doppler Ultrasound Early Diagnosis Epithelium Equipment Evaluation Event Follicle Stimulating Hormone Receptor Gene Expression Genitourinary system Glucose Goals Health Care Costs Histology Human Image Immunohistochemistry Injections Integrins Intravenous Longitudinal Studies Malignant - descriptor Malignant Female Reproductive System Neoplasm Malignant neoplasm of ovary Mechanics Microbubbles Modeling Morbidity - disease rate Nuclear Operative Surgical Procedures Ovarian Ovary Patients Physicians Predictive Value Prevalence Process Proteins Proteomics Reporting Research Resolution Scanning Screening for Ovarian Cancer Sensitivity and Specificity Serum Serum Markers Serum Proteins Signal Transduction Specificity Surface Survival Rate Testing Time Tissues Translating Transvaginal Ultrasound Ultrasonography Variant Woman diagnostic biomarker early detection biomarkers egg genetic regulatory protein glucose-regulated proteins imaging agent imaging biomarker imaging modality imaging probe improved in vivo mesothelin molecular imaging mortality neoplastic cell novel ovarian neoplasm predictive test prophylactic success targeted agent targeted imaging tumor

项目摘要

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.

摘要我们建议测试我们的靶向超声成像探针在早期检测中的有效性和特异性。经阴道超声(TVUS)分期卵巢癌(OVCA)然后，我们测试预测的有效性在一项使用产蛋母鸡的纵向研究中发现了这些探针中的一种，这是目前唯一广泛使用的自发的OVCA。OVCA是一种致命的妇科恶性肿瘤。一种有效的早期检测测试可以显著降低OVCA的高死亡率和与探查手术相关的发病率。血清CA-125、传统TVUS及其联合检测不能提高OVCA的早期诊断率。 CA-125是非特异性的，在卵巢中没有与血清CA-125升高相对应的成像靶点级别。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到卵巢肿瘤和肿瘤相关新生血管(TAN)微血管。超声目前被用于评估泌尿生殖系统肿块，以及引入分子显像剂进行早期OVCA检测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成像探针表达卵巢TAN微血管和葡萄糖调节蛋白78的激素受体表达卵巢肿瘤上皮细胞。我们在蛋鸡身上测试了这些探针。我们的初步数据支持 TVUS结合血清标志物检测早期OVCA的有效性和特异性提供原则证明。因此，在目标1中，我们建议开发新的靶向超声成像包括FSHR-和GRP78靶向成像探针在内的试剂。目标2将建立靶向成像早期OVCA的检测强度。目标3将测试这些探针检测早期阶段的能力并建立母鸡模型的假阳性率。因为很难识别患者的身份早期的OVCA和获取它们的组织，我们将使用产蛋鸡来完成我们的研究目标。由于该团队包括临床医生，我们的目的是开发这些探头供人类使用，这可能是立刻转到了诊所。