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Res Proj 3: uPAR-Targeted in Vivo Molecular Magnetic Resonance Imaging of...

Res Proj 3：uPAR 靶向体内分子磁共振成像...

基本信息

批准号：
7287005
负责人：
Hui Mao
金额：
$ 5.35万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-04-01 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7287005
关键词：
Address Affinity Anatomy Animal Model Animals Arts Binding Biocompatible Biological Markers Biological Process Biomedical Engineering Blood Circulation Breast Cancer Cell Breast Cancer Early Detection Cancer Biology Cancer Center Cancer Patient Cancer cell line Cell Surface Receptors Cell surface Cells Chemicals Chemistry Class Clinical Clinical Oncology Contrast Media Contrast Sensitivity Data Depth Detection Development Diagnostic Imaging Disease Distant Metastasis Drug Formulations Dyes Engineering Enhancers Epithelial Cells Figs - dietary Funding Future Goals Growth Human Image In Vitro Institutes Interdisciplinary Study Investigation Iron Label Lead Liver Localized Magnetic Resonance Imaging Magnetism Malignant Neoplasms Mammary Neoplasms Mammary gland Maps Medical Medical Imaging Methods Modality Modeling Modification Molecular Molecular Target Mus Nanotechnology Neoplasm Metastasis Operative Surgical Procedures Organ Pathology Pathway interactions Peptide Fragments Peptides Plasma Play Polymers Property Radiology Specialty Range Receptor Signaling Relative (related person)Research Research Personnel Resolution Resources Role Sensitivity and Specificity Serine Protease Signal Transduction Specificity Spleen Staining method Stains Surface Technology Testing Time Tissues Toxic effect Tracer Transgenic Mice Transgenic Model Translating Tumor Tissue USA Georgia Urokinase Urokinase Plasminogen Activator Receptor Western Asia Georgia Work Xenograft Model Xenograft procedure Yang angiogenesis base biomaterial compatibility cancer imaging carboxylate cell motility chemical synthesis clinical Diagnosis clinical application cytotoxicity design experience functional group imaging probe improved in vivo iron oxide malignant breast neoplasm migration molecular imaging molecular/cellular imaging nanocrystal nanoimaging nanomaterials nanoparticle nanoprobe neoplastic cell novel oncology optical imaging outcome forecast particle receptor research study size soft tissue surface coating targeted delivery tool tumor tumor growth tumor xenograft uptake

项目摘要

Project #3 of EMTIC was developed to address the critical need of early detection of breast cancer with high specificity. We have identified the urokinase plasminogen activator receptor (uPAR) as an imaging target, since it is highly expressed in human breast cancer at levels of 13,700 to 50,000 uPAR per cell relative to 2,500 uPAR per cell in normal mammary epithelial cells. The increased level of uPAR is considered to be associated with tumor aggressiveness, the presence of distant metastasis and poor prognosis. Previous studies, including work by this group, have shown that the amino terminal fragment (ATF) of uPAR is responsible for recognition and specific binding to the tumor cell surface. We propose the development of a uPAR-targeted molecular Magnetic Resonance Imaging (MRI) probe that takes advantage of our experience and ability to produce ATF in large quantites and our technology of making various formulations of superparamagnetic iron oxide (IO) nanoparticles. The surface of the IO nanoparticles has been modified with functional groups (-COOH), allowing conjugation of uPAR to the nanoparticle surface. Given the capability of tumor targeting with ATF of uPAR and MRI signal amplification with paramagnetic IO nanoparticles, we believe that such a receptor-targeted MRI probe may lead to the accumulation of the probe in tumors. Localized accumulation of ATF-conjugated magnetic IO nanoparticles must produce sufficient contrast to permit MRI detection of tumors with elevated uPAR. Our preliminary data demonstrate, for the first time, that a breast cancer targeted molecular MRI biomarker can be achieved in xenograft animal models in vivo. Our specific Aims are: 1. Developing and optimizing the method for conjugating ATF peptide to IO nanoparticles and examining the specificity of the uPAR targeting imaging probe to normal and breast cancer cells in vitro; 2. Investigating the specificity of uPAR-targeted ATF-IO nanoparticles in tumor targeting and comparison of the sensitivity of tumor imaging in mouse tumor and human tumor xenograft and transgenic models. 3. Determining the tissue/organ distribution of uPAR targeted ATF-IO nanoprobe and assessing toxicity. 4. Characterizing the imaging and contrast properties of ATF-IO nanoparticles to develop appropriate methods for using this imaging probe in uPAR-targeted breast cancer imaging. Since IO particles are biodegradable and have been used in clinical imaging, there is a strong potential that this imaging probe and imaging method are applicable in clinical applications in the future.

EMTIC项目#3的开发是为了解决早期发现高乳腺癌的迫切需要