Targeted Nanoprobes For Intraoperative optical Imaging of Breast Cancer Margins

用于乳腺癌边缘术中光学成像的靶向纳米探针

• 批准号: 7617572
• 负责人: Lily Yang
• 金额: $ 31.88万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-25 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7617572
• 关键词: 3-Dimensional; Address; Affinity; Algorithms; Anesthesia procedures; Animal Model; Animals; Area; Binding; Biodistribution; Biological Markers; Bioluminescence; Biomedical Engineering; Blood; Breast Cancer Cell; Breast Cancer Detection; Breast Cancer Model; Breast-Conserving Surgery; Cancer Biology; Cancer Patient; Cancer cell line; Clinical; Complex; Cosmetics; Detection; Development; Devices; Diagnosis; Diffuse; Disease-Free Survival; Distant; Distant Metastasis; Drug or chemical Tissue Distribution; Dyes; Endothelial Cells; Engineering; Excision; Fatty acid glycerol esters; Fiber Optics; Fibroblasts; Figs - dietary; Firefly Luciferases; Fluorescence; Freezing; Frozen Sections; Funding; Future; Goals; Growth; Human; Image; Image-Guided Surgery; Imaging Device; In Vitro; Investigation; Kidney; Label; Laboratories; Lesion; Ligands; Location; Luc Gene; Lung; Magnetic Resonance Imaging; Magnetism; Mammary Gland Parenchyma; Mammary Neoplasms; Mammary gland; Measures; Medical; Medical Imaging; Methods; Modeling; Molecular Target; Mus; Nanotechnology; Neoplasm Metastasis; Normal tissue morphology; Operative Surgical Procedures; Optical Tomography; Optics; Organ; Patients; Peptides; Preparation; Prognostic Factor; Protocols documentation; Radiation therapy; Recurrence; Research; Research Personnel; Residual Tumors; Resolution; Sensitivity and Specificity; Signal Transduction; Site; Specificity; Specimen; Spleen; Staging; Stromal Cells; Surgical Management; Survival Rate; System; Tail; Testing; Thymus Gland; Time; Tissues; Touch sensation; Translating; Tumor Tissue; Urokinase; Urokinase Plasminogen Activator Receptor; Veins; Xenograft Model; activating transcription factor; breast lumpectomy; cancer cell; cancer imaging; cellular targeting; chemical synthesis; chemotherapy; clinical application; copolymer; cyanine dye; efficacy evaluation; experience; granulocyte; imaging modality; imaging probe; improved; in vivo; instrument; instrumentation; iron oxide; macrophage; malignant breast neoplasm; molecular imaging; nanomaterials; nanoparticle; nanoprobe; neoplastic cell; novel; oncology; optical imaging; prevent; receptor binding; reconstruction; success; tissue phantom; tomography; tool; tumor

DESCRIPTION (provided by applicant): Breast-conserving surgery, or lumpectomy, is the most common surgical procedure for patients diagnosed with an early stage of invasive breast cancer. Clearly defined tumor margins and complete surgical removal of tumors are critical for preventing local recurrence and increasing disease-free survival. Currently, there is no accurate method to identify tumor margins pre- or intra-operatively. About 20% to 30% of the patients who undergo lumpectomy require additional surgery to excise any remaining tumors due to the presence of positive tumor margins. To develop a sensitive approach for detecting tumor margins in breast tissues, we propose to engineer a tumor targeted nanoparticle imaging probe by labeling a peptide containing the receptor binding domain (ATF) of urokinase plasminogen activator (uPA) with a near infrared (NIR) dye and then conjugating these complexes to a magnetic iron oxide (IO) nanoparticle. The objectives of this proposed study are: 1) to develop new NIR optical imaging nanoprobes targeting the cellular receptor for uPA; 2) to develop a sensitive fluorescence tomography system for imaging-guided surgery aimed at completely removing tumor lesions within breast tissue; and 3) to examine the effect of the optical imaging guided resection of mammary tumors on local tumor recurrence and metastasis in a mouse mammary tumor model. The development of novel tumor targeted NIR imaging nanoprobes, in combination with a sensitive and high resolution NIR fluorescence tomography system, should have great potential for determining tumor margins during surgery, preventing tumor recurrence and therefore, increasing the survival rate of breast cancer patients. PUBLIC HEALTH RELEVANCE The objective of this proposed study is to develop a novel optical imaging approach that combines tumor targeted optical imaging probes with advanced optical imaging instrumentation for the detection of breast cancer and for outlining the tumor border during breast conserving surgery. In this study, we will develop urokinase plasminogen activator receptor (uPAR) targeted near infrared (NIR) dye-labeled nanoparticles to deliver the imaging probes into breast tumors, the location and depth of the tumors will be detected using 3D diffuse fluorescence tomography. Success in this proposed study should provide us with novel optical imaging agents as well as instruments to address the urgent need for preventing tumor recurrence after breast conserving surgery and ultimately, to improve the survival rate of breast cancer patients.

描述(申请人提供)：保乳手术，或肿块切除术，是诊断为早期浸润性乳腺癌患者最常见的外科手术。明确的肿瘤边缘和完全手术切除肿瘤对于防止局部复发和提高无病生存率至关重要。目前，还没有准确的方法来确定手术前或手术中的肿瘤边缘。大约20%到30%的接受肿块切除术的患者需要额外的手术来切除任何残留的肿瘤，因为存在阳性的肿瘤边缘。为了开发一种检测乳腺组织肿瘤边缘的灵敏方法，我们提议设计一种肿瘤靶向纳米颗粒成像探针，方法是将含有尿激酶型纤溶酶原激活剂(UPA)受体结合域(ATF)的多肽与近红外(NIR)染料标记，然后将这些络合物连接到磁性氧化铁(IO)纳米颗粒上。本研究的目标是：1)开发针对uPA细胞受体的新的近红外光学成像纳米探针；2)开发一种灵敏的荧光断层成像系统，用于成像引导手术，旨在彻底去除乳腺组织内的肿瘤病变；以及3)在小鼠乳腺肿瘤模型中检测光学成像引导下的乳腺肿瘤切除对局部肿瘤复发和转移的影响。新型肿瘤靶向近红外成像纳米探针的开发，与灵敏、高分辨率的近红外荧光断层成像系统相结合，在术中确定肿瘤边缘，防止肿瘤复发，从而提高乳腺癌患者的生存率方面具有巨大的潜力。 这项拟议研究的目标是开发一种新的光学成像方法，将肿瘤靶向光学成像探针与先进的光学成像仪器相结合，用于检测乳腺癌并在保乳手术中勾勒出肿瘤边界。在这项研究中，我们将开发定位于近红外(NIR)染料标记的尿激酶型纤溶酶原激活剂受体(UPAR)纳米颗粒，将成像探针输送到乳腺肿瘤中，利用三维漫反射荧光断层扫描(3D DFCT)检测肿瘤的位置和深度。这项研究的成功将为我们提供新的光学显像剂和仪器，以满足预防乳腺癌保乳手术后肿瘤复发的迫切需要，并最终提高乳腺癌患者的存活率。