Magneto-motive ultrasound imaging using molecular specific nanoparticles

描述（由申请方提供）：皮肤恶性黑色素瘤的发生率 最严重的皮肤癌 在美国，肺癌的发病率比其他任何癌症都要高，而且这种发病率的上升预计将持续至少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。诊断时准确的分期对评估预后和确定最佳治疗策略至关重要。区域淋巴结的物理检查往往是不准确的。关于区域淋巴结状态的更明确的信息可以从选择性淋巴结清扫术（ELND）、淋巴结造影术和前哨淋巴结活检（LSNB）或细针穿刺中获得。然而，这些程序有几个主要缺点。虽然某些转移性疾病的部位在临床上可能很明显，但影像学检查必须用于发现未被怀疑的转移 几乎所有死于黑色素瘤的患者都是由于疾病扩散而死亡的。因此，影像学检查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）和超声成像是无效的，在大多数无症状的患者与阶段I或II的疾病。因此，临床上迫切需要一种广泛可用、无创且操作简单、安全且能够可靠地检测和充分地真实的诊断早期淋巴结微转移的客观成像技术。我们的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 磁动超声成像 能够在所有阶段立即和准确地评估转移性疾病的存在和程度。在MMUS成像中，靶向磁性氧化铁纳米颗粒被注射到组织中，并且超声用于可视化组织并准确评估由外部施加的磁场引起的内部组织运动。本申请的中心主题是三方面的：设计和构建磁动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，以及在组织模拟模型、3D细胞组织构建体以及最后的离体、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，皮肤癌是所有癌症中最常见的，这并不奇怪。黑素瘤 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岁女性中第二常见的癌症，也是25至30岁女性癌症死亡的主要原因。我们研究计划的总体目标是开发一种先进的、无创（或微创）的、真实的实时成像技术 磁动超声成像 评估前哨淋巴结转移，从而确定最佳治疗干预，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.