Molecular Ultrasound for Early Breast Cancer Detection

分子超声用于早期乳腺癌检测

• 批准号: 8115571
• 负责人: Juergen Karl Willmann
• 金额: $ 32.65万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-13 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8115571
• 关键词: Acoustics; Benign; Binding; Biopsy; Breast; Breast Cancer Detection; Breast Cancer Early Detection; Breast Diseases; Cancer Diagnostics; Clinic; Clinical; Clinical Trials; Core Biopsy; Data; Detection; Development; Diagnosis; Diagnostic Neoplasm Staging; Early Diagnosis; Excision; Goals; Gold; Histology; Human; Image; Image Guided Biopsy; Imagery; Intervention; Lead; Ligands; Magnetic Resonance Imaging; Malignant - descriptor; Mammary Gland Parenchyma; Mammary gland; Microbubbles; Molecular; Molecular Target; Monitor; Mus; Operative Surgical Procedures; Pathology; Patient Care; Patients; Pattern; Pharmacotherapy; Protocols documentation; Research Proposals; Resolution; Schedule; Screening procedure; Sensitivity and Specificity; Signal Transduction; Simulate; Staging; Subgroup; Techniques; Testing; Tissues; Toxic effect; Transgenic Mice; Transgenic Organisms; Translating; Translations; Tumor Angiogenesis; Ultrasonics; Ultrasonography; Vascular Endothelial Cell; Vascular Endothelial Growth Factor Receptor-2; Woman; angiogenesis; base; breast cancer diagnosis; breast lesion; cost; design; diagnostic accuracy; efficacy trial; high risk; imaging modality; improved; in vivo; irradiation; malignant breast neoplasm; molecular imaging; molecular marker; molecular pathology; mouse model; next generation; novel; particle; pre-clinical; receptor expression; response; tool; tumor

DESCRIPTION (provided by applicant): Breast cancer early detection can substantially improve patient survival. Ultrasound is one of the primary imaging approaches to diagnose breast diseases and fulfills many prerequisites as an ideal imaging and screening tool for breast cancer early detection: It is non-invasive and relatively cheap compared to other imaging modalities; it does not use ionizing irradiation; it has a high spatial and temporal resolution and is routinely available in most clinical imaging departments worldwide. However, ultrasound often lacks the sensitivity and specificity to detect breast cancer at an early stage. In this proposed study, we will combine the advantages of ultrasound with the advantages of molecular imaging through use of molecularly targeted ultrasound contrast microbubbles. This modified targeted contrast-enhanced ultrasound imaging strategy (molecular ultrasound imaging), may provide a quantitative and objective imaging approach for earlier detection of breast cancer. We will test newly developed clinically translatable micro bubbles that are targeted to the human kinase insert domain receptor (KDR), which has been shown to be over expressed on angiogenic vessels in breast cancer. In longitudinal screening exams in transgenic mice with mammary glands progressing from normal breast tissue to invasive breast cancer, diagnostic accuracy of screening ultrasound using KDR-targeted contrast micro bubbles will be assessed in vivo. Molecular ultrasound imaging data will be quantitatively correlated with KDR expression in tumor vessels and with tumor histology. Following ongoing toxicity studies on KDR-targeted micro bubbles in patients, we will perform a first ever clinical feasibility and efficacy trial on KDR-targeted molecular ultrasound imaging in women with various breast pathologies, using histology as the gold standard. Finally, we will further develop and refine molecular ultrasound imaging for early breast cancer detection by designing next generation contrast micro bubbles targeted to breast cancer specific molecular targets. Based on successful study results, we anticipate rapid translation of this technique into the clinic to improve patient survival and patient care by diagnosing breast cancer at an earlier stage. PUBLIC HEALTH RELEVANCE: Current strategies for the diagnosis of early breast cancer have major limitations leading to delayed or missed diagnoses. In this research proposal, we will test the accuracy of a new targeted ultrasound imaging approach that allows detection of molecular alterations in tumor vessels of early stage breast cancer. The successful completion of our aims will lead to the development of a new imaging approach that can be used to more accurately diagnose breast cancer at an early, still curable stage.

描述（由申请人提供）：乳腺癌早期检测可以显着提高患者的生存率。超声是诊断乳腺疾病的主要成像方法之一，作为乳腺癌早期检测的理想成像和筛查工具，满足许多先决条件：它是非侵入性的，与其他成像方式相比相对便宜；不使用电离辐射；它具有高空间和时间分辨率，并且在全球大多数临床成像部门中常规可用。然而，超声波通常缺乏早期检测乳腺癌的敏感性和特异性。在这项拟议的研究中，我们将通过使用分子靶向超声造影微泡将超声的优点与分子成像的优点结合起来。这种改进的靶向对比增强超声成像策略（分子超声成像）可以为乳腺癌的早期检测提供定量和客观的成像方法。我们将测试新开发的临床可翻译微泡，这些微泡针对人类激酶插入结构域受体（KDR），该受体已被证明在乳腺癌的血管生成血管中过度表达。在对乳腺从正常乳腺组织进展为浸润性乳腺癌的转基因小鼠进行纵向筛查检查时，将在体内评估使用 KDR 靶向对比微泡筛查超声的诊断准确性。分子超声成像数据将与肿瘤血管中的 KDR 表达和肿瘤组织学定量相关。继对患者中 KDR 靶向微泡正在进行的毒性研究之后，我们将使用组织学作为金标准，对患有各种乳腺疾病的女性进行首次 KDR 靶向分子超声成像的临床可行性和功效试验。最后，我们将通过设计针对乳腺癌特定分子靶标的下一代对比微泡，进一步开发和完善用于早期乳腺癌检测的分子超声成像。基于成功的研究结果，我们预计该技术将迅速转化为临床，通过早期诊断乳腺癌来提高患者的生存率和患者护理。 公共卫生相关性：当前早期乳腺癌的诊断策略存在重大局限性，导致诊断延迟或漏诊。在这项研究计划中，我们将测试一种新的靶向超声成像方法的准确性，该方法可以检测早期乳腺癌肿瘤血管的分子变化。我们目标的成功实现将导致一种新的成像方法的开发，该方法可用于在早期、仍可治愈的阶段更准确地诊断乳腺癌。