权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

uPAR Targeted in Vivo Molecular Magnetic Resonance Imaging of....

uPAR 靶向体内分子磁共振成像......

基本信息

批准号：
8135468
负责人：
Hui Mao
金额：
$ 21.84万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8135468
关键词：
Address Affinity Anatomy Animals Area Arts Binding Biodistribution Biological Markers Biological Process Biomedical Engineering Blood Circulation Breast Cancer Cell Breast Cancer Detection Breast Cancer Early Detection Breast Cancer Model Cancer Biology Cancer Center Cancer Patient Cell Communication Cell Surface Receptors Cell surface Cells Chemicals Chemistry Clinical Clinical Oncology Contrast Media Contrast Sensitivity Data Detection Development Diagnostic Imaging Disease Distant Metastasis Drug Formulations Drug Kinetics Dyes Enhancers Epithelial Cells Figs - dietary Funding Future Goals Human Image In Vitro Institutes Interdisciplinary Study Investigation Label Lead Liver Magnetic Resonance Imaging Magnetism Malignant Neoplasms Mammary Neoplasms Mammary gland Maps Medical Medical Imaging Methods Modeling Modification Molecular Molecular Target Mus Nanotechnology Neoplasm Metastasis Operative Surgical Procedures Organ Pathway interactions Peptide Fragments Peptides Plasma Play Polymers Property Radiology Specialty Receptor Cell Relative (related person)Research Research Personnel Resolution Resources Role Sensitivity and Specificity Signal Transduction Specificity Spleen Surface Technology Testing Time Tissues Toxic effect Transgenic Mice Transgenic Organisms Translating Tumor Tissue Urokinase Urokinase Plasminogen Activator Receptor Work Xenograft Model Yang angiogenesis base biomaterial compatibility cancer cell cancer imaging carboxyl group cell motility chemical synthesis clinical Diagnosis clinical application cytotoxicity design experience imaging modality imaging probe improved in vivo iron oxide malignant breast neoplasm molecular imaging molecular/cellular imaging nanocrystal nanomaterials nanoparticle nanoprobe neoplastic cell novel oncology optical imaging outcome forecast particle receptor research study soft tissue surface coating tumor tumor xenograft uptake

项目摘要

Project #3 is developed to address the critical needs of novel molecular imaging approaches for early detection of breast cancer. We have identified a moleculer target, urokinase plasminogen activator receptor (uPAR) for receptor targeted MR imaging of breast cancer. uPAR is highly expressed in human breast cancer cells at levels of 14,000 to 500,000 uPAR/cell relative to 2,500/cell in normal mammary epithelial cells. An increased level of uPAR is considered to be associated with tumor aggressiveness, the presence of distant metastasis and poor prognosis. Previous studies have shown that the amino terminal fragment (ATF) peptide of uPAR is responsible for recognition and specific binding to the tumor cell. We propose to develop a uPAR-targeted paramagnetic iron oxide (IO) nanoparticle imaging probe for molecular Magnetic Resolnance Imaging (MRI) of breast cancer. This imaging strategy takes advantages of our experience and ability to produce the ATF in large quantity, our technology of formulating and synethsizing IO nanoparticles for optimal MRI contrast via T2- shortening effect and the chemistry of functionalizing particle surface for conjugating tumor targeting peptides. Given the capability of uPAR targeting with the ATF peptide and strong MRI contrast induced by IO nanoparticles, we hypothesize that this receptor-targeted MRI probe may lead to the accumulation of ATF conjugated IO nanoparticles in the tumor, producing sufficient contrast to detect tumors with elevated level of uPAR. Our preliminary data demonstrated that this breast cancer targeted molecular MRI can be achieved in a mouse mammary tumor model. Specific aims of this project are: 1) to optimize the method for conjugating the ATF peptide to IO nanoparticles and to examine the specificity of the uPAR targeted-imaging probe in normal and breast cancer cells in vitro; 2) to investigate the specificity and sensitivity of uPAR targeted ATF-IO nanoparticles in detection of breast cancer using mouse mammary tumor, human tumor xenograft, and transgenic tumor models; 3) to examine the biodistribution and toxicity of ATF-IO nanoparticles; and 4) to characterize MRI contrast properties of ATF-IO nanoparticles and to develop imaging methods appropriate for imaging of receptor targeted IO nanoprobes in vivo. It is anticipated that this tumor receptor-targeted MRI probe and imaging method can improve the specificity of breast cancer imaging be translated to clinical applications in the future.

项目#3的开发是为了满足早期诊断的新型分子成像方法的关键需求。乳腺癌的诊断我们已经确定了一个分子靶点，尿激酶纤溶酶原激活剂受体（uPAR）用于乳腺癌的受体靶向MR成像。uPAR高表达于人乳腺癌细胞在14，000至500，000 uPAR/细胞的水平，相对于正常人2，500 uPAR/细胞乳腺上皮细胞。uPAR水平升高被认为与肿瘤相关。侵袭性、远处转移和预后差。先前的研究表明 uPAR的氨基末端片段（ATF）肽负责识别和特异性识别uPAR。与肿瘤细胞结合。我们建议开发一种靶向uPAR的顺磁性氧化铁（IO）用于乳腺癌的分子磁分辨成像（MRI）的纳米颗粒成像探针。这成像策略利用了我们的经验和大量生产ATF的能力，我们的技术，制定和合成IO纳米粒子的最佳MRI对比度，通过T2- 缩短效应和用于缀合肿瘤靶向的功能化颗粒表面的化学缩氨酸鉴于ATF肽靶向uPAR的能力和诱导的强MRI对比度，通过IO纳米颗粒，我们假设这种受体靶向的MRI探针可能导致 ATF缀合的IO纳米颗粒在肿瘤中的积累，产生足够的对比度以检测 uPAR水平升高的肿瘤。我们的初步数据表明，这种乳腺癌可以在小鼠乳腺肿瘤模型中实现靶向分子MRI。具体目标项目是：1）优化用于将ATF肽缀合至IO纳米颗粒的方法，检测uPAR靶向成像探针在体外正常和乳腺癌细胞中的特异性; 2)研究靶向uPAR的ATF-IO纳米颗粒在检测使用小鼠乳腺肿瘤、人肿瘤异种移植物和转基因肿瘤模型的乳腺癌; 3)检查ATF-IO纳米颗粒的生物分布和毒性;以及4）表征MRI ATF-IO纳米颗粒的对比度特性，并开发适合于成像的成像方法受体靶向IO纳米探针的体内研究。预期这种肿瘤受体靶向MRI探针而影像学方法可以提高乳腺癌影像学的特异性，将其转化为临床应用在未来。