A multimodal imaging system and targeted nanoprobes for image-guided treatment of breast cancer

用于乳腺癌图像引导治疗的多模态成像系统和靶向纳米探针

基本信息

  • 批准号:
    9513881
  • 负责人:
  • 金额:
    $ 60.57万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-09-15 至 2020-06-30
  • 项目状态:
    已结题

项目摘要

Principal Investigator/Program Director (Last, First, Middle): Jiang, Huabei /Yang, Lily About 20% of breast cancers have a distinct signature of estrogen receptor (ER), progesterone receptor (PR) and Her-2/Neu negative. Over 60% of triple negative breast cancer (TNBC) are highly resistant to chemotherapy and have a poor prognosis. More than 50% of the TNBC patients with drug resistant residual tumors after pre-operative chemotherapy developed local and distant recurrent tumor within three years after surgery and most of them died due to tumor recurrence. This unmet clinical challenge underscores an urgent need for novel approaches for effective treatment of drug resistant TNBCs. One of the approaches that may have the most impact is to develop specific and sensitive image-guided surgery to completely remove small drug resistant tumor lesions and tumor cell involved lymph nodes. We hypothesize that a novel multimodal approach that integrates photoacoustic tomography (PAT) and fluorescence molecular tomography (FMT) in combination with multiplexed tumor biomarker targeted imaging probes can most accurately detect small drug resistant breast tumors and tumor involved lymph nodes in 3D at the microns resolution scale, thus serving as an ideal guidance for surgery of breast cancer. This first ever integrated PAT and FMT device will allow us to three-dimensionally detect small tumors (~30µm) at a depth of ~3cm, which are previously unachievable. The goal of this proposal is to advance this cutting-edge imaging technology to engineer a multimodal approach that integrates PAT and FMT into a single endoscope for optimized 3D detection of breast cancer through the use of microelectromechanical systems (MEMS). In particular, we will use multiplexed “smart” nanoprobes that are targeted to cellular receptors that are highly expressed in TNBC cancer cells, especially aggressive drug resistant cells, such as urokinase plasminogen activator receptor (uPAR) and insulin-like growth factor 1 receptor (IGF-1R) to realize multiplexed specific and sensitive molecular imaging of heterogeneous TNBC cells. A marked pathological feature of TNBC is the presence of extensive tumor stroma expressing high levels of uPAR and IGF1R. Targeting those two receptors further enhances the sensitivity of detection of small tumors (< 1 mm) with poor tumor vessels. Beyond image-guided surgery of breast cancer, we anticipate the technology to be much more broadly applicable to other pressing healthcare problems such as endoscopic detection of esophageal, colon, pancreatic and prostate cancers. This application has put together a truly multi- disciplinary research team involving investigators in imaging, MEMS, probe synthesis, cancer biology, and surgical oncology. With a long-term goal of translating the proposed technology into a clinical application, we propose to complete the following specific aims: (1) To develop a MEMS-based photoacoustic tomography system for intraoperative tumor imaging in real time; (2) To develop a MEMS based multi-modal PAT/FMT system for intraoperative tumor imaging in real time; (3) To validate and optimize the MEMS-PAT and MEMS- PAT/FMT systems using phantom and in vivo experiments; and (4) To determine sensitivity and specificity of PAT and PAT/FMT imaging using the multiplexed targeted imaging probes and evaluate the efficacy of in vivo PAT- and PAT/FMT-guided surgery in two orthotopic human TNBC patient tissue derived tumor xenograft (PDX) models in nude mice.
主要研究者/项目负责人(末、中、首):蒋华北/杨莉莉 大约20%的乳腺癌具有明显的雌激素受体(ER)、孕激素受体(PR)特征 Her-2/Neu阴性。超过60%的三阴性乳腺癌(TNBC)对化疗具有高度耐药性。 化疗,预后差。超过50%的TNBC患者有耐药残留 术前化疗后的肿瘤在术后三年内发生局部和远处复发 大多数患者因肿瘤复发而死亡。这一未得到满足的临床挑战强调了一个紧迫的问题, 需要有效治疗耐药性TNBC的新方法。其中一种方法可能 最有影响的是制定具体的和敏感的图像引导手术,以彻底消除小 耐药肿瘤病变和肿瘤细胞累及淋巴结。我们假设一种新型的多模态 该方法集成了光声层析成像(PAT)和荧光分子层析成像(FMT), 与多重肿瘤生物标志物靶向成像探针的组合可以最准确地检测小药物 耐药乳腺肿瘤和肿瘤涉及的淋巴结在三维微米分辨率尺度,从而作为 是乳腺癌手术的理想指导。这是首款集成PAT和FMT的设备, 三维检测小肿瘤(~30µm),深度约3 cm,这是以前无法实现的。的 该提案的目标是推进这一尖端成像技术,以设计一种多模态方法 将PAT和FMT集成到单个内窥镜中,通过 微机电系统(MEMS)。特别是,我们将使用多路复用的“智能”纳米探针, 靶向TNBC癌细胞中高度表达的细胞受体,特别是侵袭性药物 耐药细胞,如尿激酶纤溶酶原激活物受体(uPAR)和胰岛素样生长因子1 受体(IGF-1 R)的特异性和灵敏性,以实现异质TNBC细胞的多重特异性和灵敏的分子成像。 TNBC的显著病理学特征是存在表达高水平TNBC的广泛肿瘤基质。 uPAR和IGF 1 R。靶向这两种受体进一步提高了检测小肿瘤的灵敏度 (< 1 mm),肿瘤血管较差。除了乳腺癌的图像引导手术,我们预计 该技术将更广泛地应用于其他紧迫的医疗保健问题,如内窥镜检查, 食管癌、结肠癌、胰腺癌和前列腺癌的检测。这个应用程序已经把一个真正的多- 学科研究团队,包括成像,MEMS,探针合成,癌症生物学和 外科肿瘤学我们的长期目标是将所提出的技术转化为临床应用, 本文拟完成以下具体目标:(1)研制基于MEMS的光声层析成像系统 研制了一种基于MEMS的多模态PAT/FMT系统 (3)验证和优化MEMS-PAT和MEMS- PAT/FMT系统使用体模和体内实验;和(4)为了确定灵敏度和特异性, 使用多重靶向成像探针进行PAT和PAT/FMT成像,并评估体内 PAT和PAT/FMT引导的两例原位人TNBC患者组织源性肿瘤异种移植手术 (PDX)裸鼠模型。

项目成果

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HUABEI JIANG其他文献

HUABEI JIANG的其他文献

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{{ truncateString('HUABEI JIANG', 18)}}的其他基金

MEMS Based Intraoperative Photoacoustic Imaging
基于 MEMS 的术中光声成像
  • 批准号:
    8458060
  • 财政年份:
    2012
  • 资助金额:
    $ 60.57万
  • 项目类别:
MEMS Based Intraoperative Photoacoustic Imaging
基于 MEMS 的术中光声成像
  • 批准号:
    8302081
  • 财政年份:
    2012
  • 资助金额:
    $ 60.57万
  • 项目类别:
Noninvasive Functional and Cellular Imaging of Epilepsy
癫痫的无创功能和细胞成像
  • 批准号:
    8265960
  • 财政年份:
    2010
  • 资助金额:
    $ 60.57万
  • 项目类别:
Noninvasive Functional and Cellular Imaging of Epilepsy
癫痫的无创功能和细胞成像
  • 批准号:
    8415577
  • 财政年份:
    2010
  • 资助金额:
    $ 60.57万
  • 项目类别:
Noninvasive Functional and Cellular Imaging of Epilepsy
癫痫的无创功能和细胞成像
  • 批准号:
    8020033
  • 财政年份:
    2010
  • 资助金额:
    $ 60.57万
  • 项目类别:
Noninvasive Functional and Cellular Imaging of Epilepsy
癫痫的无创功能和细胞成像
  • 批准号:
    7865824
  • 财政年份:
    2010
  • 资助金额:
    $ 60.57万
  • 项目类别:
Diffuse Optical Tomography of Osteoarthritis
骨关节炎的漫反射光学断层扫描
  • 批准号:
    7227090
  • 财政年份:
    2003
  • 资助金额:
    $ 60.57万
  • 项目类别:
Diffuse Optical Tomography of Osteoarthritis
骨关节炎的漫反射光学断层扫描
  • 批准号:
    7111041
  • 财政年份:
    2003
  • 资助金额:
    $ 60.57万
  • 项目类别:
Diffuse Optical Tomography of Osteoarthritis
骨关节炎的漫反射光学断层扫描
  • 批准号:
    6891945
  • 财政年份:
    2003
  • 资助金额:
    $ 60.57万
  • 项目类别:
Diffuse Optical Tomography of Osteoarthritis
骨关节炎的漫反射光学断层扫描
  • 批准号:
    6679516
  • 财政年份:
    2003
  • 资助金额:
    $ 60.57万
  • 项目类别:

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