Magneto-motive ultrasound imaging using molecular specific nanoparticles

描述(申请人提供)：皮肤恶性黑色素瘤是皮肤癌中最严重的一种，其发病率比美国其他任何癌症的增长速度都快，预计这种上升的发病率将至少在未来20年内持续。黑色素瘤患者的预后取决于原发肿瘤的组织学和转移性疾病的存在和程度。诊断时准确的分期对于评估预后和确定最佳治疗策略是重要的。对区域淋巴结的体检往往不准确。有关区域淋巴结状况的更明确信息可通过选择性淋巴清扫术(ELND)、前哨淋巴结活检术(LSNB)或细针抽吸获得。然而，这些程序有几个主要的缺点。虽然一些转移疾病的部位在临床上可能是明显的，但必须使用成像来检测意外转移，几乎所有死于黑色素瘤的患者都患有播散性疾病。因此，影像研究是评估局限性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或II期疾病的无症状患者无效。因此，临床迫切需要一种可广泛应用、无创、操作简单、安全、能够可靠地实时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、最小限度的非侵入性、分子特异性成像技术磁动超声(MMUS)成像，能够在所有阶段立即准确地评估转移疾病的存在和程度。在MMUS成像中，目标磁性氧化铁纳米颗粒被注射到组织中，超声波被用于可视化组织和准确地评估外部磁场诱导的内部组织运动。目前应用的中心主题有三个：设计和建造磁动型超声成像系统的实验室原型，为MMUS成像系统开发分子敏感的造影剂，以及初步测试所开发的MMUS成像技术在组织模体、3D细胞组织结构以及小动物癌症体外、体外和体内模型中的应用。皮肤是人体最大的器官，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皮肤细胞的癌症，称为黑素细胞，是最致命的皮肤癌，占皮肤癌死亡人数的79%。黑色素瘤目前在美国男性中排名第六，在美国女性中排名第七。确诊时的中位年龄在45岁至55岁之间，尽管25%的病例发生在40岁之前的个人。在20岁至35岁的女性中，它是第二常见的癌症，在25岁至30岁的女性中，它是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)的实时成像技术--磁动力超声(MMUS)成像，以评估前哨淋巴结转移，从而确定最佳的治疗干预措施，如有必要，包括立即治疗。

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.