Molecular Ultrasound for Early Breast Cancer Detection

描述（申请人提供）：乳腺癌的早期发现可以大大提高患者的生存率。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，它满足了许多先决条件：与其他成像方式相比，它是非侵入性的，相对便宜；它不使用电离辐射；它具有很高的空间和时间分辨率，在世界上大多数临床成像部门都是常规可用的。然而，超声往往缺乏在早期发现乳腺癌的敏感性和特异性。在本研究中，我们将通过使用分子靶向超声造影剂微泡，将超声的优势与分子成像的优势结合起来。这种改进的靶向对比增强超声成像策略（分子超声成像），可能为乳腺癌的早期发现提供一种定量、客观的成像方法。我们将测试新开发的临床可翻译的微泡，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上过度表达。在乳腺从正常乳腺组织向浸润性乳腺癌进展的转基因小鼠的纵向筛查检查中，将在体内评估kdr靶向造影剂微泡筛查超声的诊断准确性。分子超声成像数据将定量地与KDR在肿瘤血管中的表达和肿瘤组织学相关。在对患者进行kdr靶向微泡的毒性研究之后，我们将以组织学为金标准，对患有各种乳腺病变的女性进行kdr靶向分子超声成像的临床可行性和疗效试验。最后，我们将通过设计针对乳腺癌特异性分子靶点的下一代造影剂微泡，进一步发展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，我们期待这项技术迅速转化为临床，通过早期诊断乳腺癌来提高患者的生存率和患者护理。

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.