Magneto-motive ultrasound imaging using molecular specific nanoparticles

描述（由申请人提供）：在美国，最严重的皮肤癌形式——皮肤恶性黑色素瘤的发病率增长速度超过任何其他癌症，预计这种上升的发病率将至少持续20年。黑色素瘤患者的预后取决于原发肿瘤的组织学以及转移性疾病的存在和程度。准确的诊断分期对于评估预后和确定最佳治疗策略非常重要。局部淋巴结的体格检查常常不准确。选择性淋巴结清扫（ELND）、前哨淋巴结活检淋巴显像（LSNB）或细针穿刺可获得更明确的区域淋巴结状态信息。然而，这些程序有几个主要的缺点。尽管一些转移性疾病的部位在临床上可能是明显的，但影像学必须用于检测未被怀疑的转移，几乎所有死于黑色素瘤的患者都死于弥散性疾病。因此，影像学研究是评估局部和晚期黑色素瘤患者的重要组成部分。然而，目前的成像技术，包括计算机断层扫描（CT）、磁共振成像（MRI）、正电子发射断层扫描（PET）和超声成像，对大多数I期或II期无症状患者无效。因此，临床迫切需要一种广泛可用、无创、操作简单、安全、能够实时可靠地检测和充分诊断早期淋巴结微转移的客观成像技术。我们研究计划的总体目标是开发一种体内、微创、分子特异性成像技术磁动机超声（MMUS）成像，能够在所有阶段立即准确地评估转移性疾病的存在和程度。在MMUS成像中，将有针对性的磁性氧化铁纳米颗粒注射到组织中，利用超声波对组织进行可视化，并准确评估由外部施加的磁场引起的组织内部运动。目前申请的中心主题是三个方面：设计和构建磁动机超声成像系统的实验室原型，开发用于MMUS成像系统的分子敏感造影剂，并在组织模拟模型，3D细胞组织构建以及最后在离体，体外和体内小动物癌症模型中初步测试所开发的MMUS成像技术。皮肤是人体最大的器官，所以皮肤癌是所有癌症中最常见的也就不足为奇了。黑色素瘤是一种始于黑色素细胞的癌症，是最致命的皮肤癌，占皮肤癌死亡人数的79%。黑色素瘤目前是美国男性第六大常见癌症，美国女性第七大常见癌症。诊断时的中位年龄在45岁至55岁之间，尽管25%的病例发生在40岁之前。它是20至35岁女性中第二大常见癌症，也是25至30岁女性癌症死亡的主要原因。我们的研究计划的总体目标是开发一种先进的，无创的（或微创的），实时成像技术磁动机超声（MMUS）成像来评估前哨淋巴结转移，从而确定最佳的治疗干预措施，包括必要时立即治疗。

DESCRIPTION (provided by applicant): The incidence of malignant melanoma of the skin the most serious form of skin cancer is increasing faster than that of any other cancer in the United States, and this rising incidence is expected to continue for at least the next 20 years. The prognosis for patients with melanoma is determined by the histology of the primary tumor and by the presence and extent of metastatic disease. Accurate staging at diagnosis is important to assess the prognosis and to determine best therapeutic strategy. The physical examination of regional lymph nodes is often inaccurate. More definitive information about the status of the regional nodes can be obtained from elective lymph node dissection (ELND), lymphoscintigraphy with sentinel node biopsy (LSNB), or fine needle aspiration. However, there are several major drawbacks of these procedures. Although some sites of metastatic disease may be clinically apparent, imaging must be used to detect unsuspected metastases almost all patients who die from melanoma do so with disseminated disease. Imaging studies are, therefore, an important component of the evaluation of patients with both localized and advanced melanoma. However, current imaging techniques including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and ultrasound imaging are ineffective in majority of asymptomatic patients with stage I or II disease. Therefore, there is an urgent and definite clinical need for an objective imaging technique that is widely available, is noninvasive and simple to perform, is safe, and can reliably detect and adequately diagnose early lymph node micro-metastases in real- time. The overall goal of our research program is to develop an in-vivo, minimally noninvasive, molecular specific imaging technology magneto-motive ultrasound (MMUS) imaging capable of immediate and accurate assessment of presence and extent of metastatic disease at all stages. In MMUS imaging, the targeted magnetic iron oxide nanoparticles are injected into the tissue and the ultrasound is used both to visualize the tissue and to accurately evaluate the internal tissue motion induced by the externally applied magnetic field. The central theme of the current application is threefold: to design and build a laboratory prototype of the magneto-motive ultrasound imaging system, to develop molecularly sensitive contrast agent for MMUS imaging system, and to initially test the developed MMUS imaging technology in tissue-mimicking phantoms, 3D cell tissue constructs and, finally, small animal cancer model ex-vivo, in vitro and in vivo. The skin is the largest organ in the body, and it is not surprising that cancer of the skin is the most common of all cancers. Melanoma a cancer that begins in skin cells called melanocytes is the most deadly skin cancer, accounting for 79% of skin cancer deaths. Melanoma is currently the sixth most common cancer in American men and the seventh most common in American women. The median age at diagnosis is between 45 and 55, although 25% of cases occur in individuals before age 40. It is the second most common cancer in women between the ages of 20 and 35, and the leading cause of cancer death in women ages 25 to 30. The overall goal of our research program is to develop an advanced, noninvasive (or minimally invasive), real- time imaging technique magneto-motive ultrasound (MMUS) imaging to assess sentinel lymph node metastases thus identifying the best therapeutic intervention including immediate therapy if necessary.