Optical Systems for In Vivo Molecular Imaging of Cancer

用于癌症体内分子成像的光学系统

基本信息

批准号：
7235589
负责人：
Rebecca R. Richards-Kortum
金额：
$ 146.42万
依托单位：
RICE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-08-01 至 2009-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7235589
关键词：
Address Affect Animal Model Architecture Award Binding Bioinformatics Biological Biological Markers Biology Biomedical Engineering Blood Vessels British Columbia Carcinoma Cause of Death Cells Cellular Morphology Cervical Cervix Uteri Chemicals Chemoprevention Clinical Clinical Data Clinical Research Clinical Trials Clinical Trials Design Collaborations Commit Complex Confocal Microscopy Contracts Contrast Media Coupled Cultured Cells DNA DNA Sequence Data Depth Detection Developed Countries Developing Countries Development Diagnosis Discipline Disease Doctor of Philosophy Drug Formulations Early Diagnosis Endopeptidases Engineering Epidemiologist Epidermal Growth Factor Receptor Epithelial Epithelial Cells Epithelium Event Facility Construction Funding Category Fiber Optics Fluorescence Fluorescent Dyes Future Gene Pool Genetic Transcription Genome Genomics Goals Gynecologic Head and neck structure Health Health Sciences Histology Human Image Imaging Device Immunotherapeutic agent In Vitro Incidence Individual Integrins Joints Knowledge Lesion Life Light Lung MRI Scans Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of cervix uteri Malignant neoplasm of lung Medical Genetics Medicine Messenger RNA Metabolism Metals Methods Microscope Microscopy Modality Modeling Molecular Molecular Analysis Molecular Probes Molecular Profiling Monitor Morphology Mouth Neoplasms Movement Neoplasms Neoplasms in Vascular Tissue Nuclear Operating Rooms Optics Oral Oral cavity Organ Organ Culture Techniques Peer Review Peptide Hydrolases Peptides Phage Display Phase Phase I/II Trial Postdoctoral Fellow Premalignant Prevention Principal Investigator Process Proteomics Protocols documentation Public Health Publications Quantum Dots Radiation Range Reaction Time Research Design Research Project Grants Resolution Risk SAGE Library Safety Science Screening procedure Semiconductors Site Small Nuclear Ribonucleoprotein Polypeptide F Smooth Muscle Actin Staining Method Source Staging Staining method Stains Students Supervision Surface Surveys System Techniques Technology Telomerase Testing Texas Therapeutic Agents Time Tissues Topical application Training Translations Universities University of Texas M D Anderson Cancer Center Validation Vascular Endothelium Veterinarians Work X-Ray Computed Tomography abstracting austin base cancer classification cancer genomics cancer imaging cancer prevention cancer therapy cancer type carcinogenesis combinatorial cost design digital imaging experience extracellular functional genomics gene-radiation therapy human subject improved in vivo interdisciplinary collaboration intraepithelial molecular imaging mortality nanoparticle neoplastic cell novel optical imaging prevention clinical trial programs receptor response rosin telomere therapeutic protein tissue culture tool tumor uptake

Address Affect Animal Model Architecture Award Binding Bioinformatics Biological Biological Markers Biology Biomedical Engineering Blood Vessels British Columbia Carcinoma Cause of Death Cells Cellular Morphology Cervical Cervix Uteri Chemicals Chemoprevention Clinical Clinical Data Clinical Research Clinical Trials Clinical Trials Design Collaborations Commit Complex Confocal Microscopy Contracts Contrast Media Coupled Cultured Cells DNA DNA Sequence Data Depth Detection Developed Countries Developing Countries Development Diagnosis Discipline Disease Doctor of Philosophy Drug Formulations Early Diagnosis Endopeptidases Engineering Epidemiologist Epidermal Growth Factor Receptor Epithelial Epithelial Cells Epithelium Event Facility Construction Funding Category Fiber Optics Fluorescence Fluorescent Dyes Future Gene Pool Genetic Transcription Genome Genomics Goals Gynecologic Head and neck structure Health Health Sciences Histology Human Image Imaging Device Immunotherapeutic agent In Vitro Incidence Individual Integrins Joints Knowledge Lesion Life Light Lung MRI Scans Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of cervix uteri Malignant neoplasm of lung Medical Genetics Medicine Messenger RNA Metabolism Metals Methods Microscope Microscopy Modality Modeling Molecular Molecular Analysis Molecular Probes Molecular Profiling Monitor Morphology Mouth Neoplasms Movement Neoplasms Neoplasms in Vascular Tissue Nuclear Operating Rooms Optics Oral Oral cavity Organ Organ Culture Techniques Peer Review Peptide Hydrolases Peptides Phage Display Phase Phase I/II Trial Postdoctoral Fellow Premalignant Prevention Principal Investigator Process Proteomics Protocols documentation Public Health Publications Quantum Dots Radiation Range Reaction Time Research Design Research Project Grants Resolution Risk SAGE Library Safety Science Screening procedure Semiconductors Site Small Nuclear Ribonucleoprotein Polypeptide F Smooth Muscle Actin Staining Method Source Staging Staining method Stains Students Supervision Surface Surveys System Techniques Technology Telomerase Testing Texas Therapeutic Agents Time Tissues Topical application Training Translations Universities University of Texas M D Anderson Cancer Center Validation Vascular Endothelium Veterinarians Work X-Ray Computed Tomography abstracting austin base cancer classification cancer genomics cancer imaging cancer prevention cancer therapy cancer type carcinogenesis combinatorial cost design digital imaging experience extracellular functional genomics gene-radiation therapy human subject improved in vivo interdisciplinary collaboration intraepithelial molecular imaging mortality nanoparticle neoplastic cell novel optical imaging prevention clinical trial programs receptor response rosin telomere therapeutic protein tissue culture tool tumor uptake

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项目摘要

DESCRIPTION (provided by applicant): Cancer is a major public health problem. Currently, classification of cancer is based on phenotypic markers. The identification of unique molecular markers of cancer has led to development of new molecular cancer therapies. Movement toward a molecular characterization of cancer would have important clinical benefits, including (1) detecting cancer earlier, (2) predicting risk of precancerous lesion progression, (3) detecting margins in the operating room in real time, (4) selecting molecular therapy rationally and (5) monitoring response to therapy in rear time at a molecular level. Imaging the molecular features of cancer requires molecular-specific contrast agents which can safely be used in vivo as well as cost-effective imaging systems to rapidly and non-invasively image the uptake, distribution and binding of these agents in vivo. Radiographic imaging modalities such as CT and MRI, although useful for delineating the deep extent of advanced carcinomas, are not sufficiently sensitive to detect small, intraepithelial lesions. Optical imaging is a new modality which enables real time, high resolution imaging of epithelial tissue. Optical imaging systems are inexpensive, robust and portable. Optical imaging systems are ideally suited for early detection of intraepithelial disease and to assess tumor margins and response to therapy. The goal of this proposal is to integrate development of optical imaging systems and contrast agents with advances in functional genomics. We will develop molecular-specific, optically active contrast agents that can be applied topically. We will also develop inexpensive, rugged and portable imaging systems to monitor the three-dimensional profile of targeted biomarkers. These contrast agents and imaging systems will have broad applicability to many types of cancer; here, we will develop and test agents and imaging systems for the cervix, oral cavity and the lung, which represent more than 20% of both tumor incidence and mortality worldwide. We will test the safety and efficacy of these contrast agents and imaging systems in animal models, providing data to support phase I and II clinical trials. The aims of this proposal are to: (1) Develop optically active contrast agents to target four molecular signatures of neoplasia, including EGFR, MMP, telomerase and alpha v integrin; (2) to identify promising new biomarkers for which contrast agents will be developed using SAGE libraries, and to identify promising molecular probes for novel contrast agents using combinatorial methods; (3) to develop inexpensive, portable optical systems to image the morphologic and molecular signatures of neoplasia noninvasively in real time; and (4) to test these agents, delivery formulations and imaging systems in living biological systems of progressively increasing complexity. (5) Our final aim is to integrate these studies to develop a miniature imaging system, which when coupled with the contrast agents developed here, can be used for real time, molecular detection of neoplasia and to monitor, at the molecular level, whether a lesion is responding to therapy.

描述（由申请人提供）：癌症是一个主要的公共卫生问题。目前，癌症的分类基于表型标记。鉴定癌症的独特分子标记已导致新分子癌疗法的发展。朝着癌症的分子表征的运动将具有重要的临床益处，包括（1）早期检测癌症，（2）预测癌前病变进展的风险，（（3）实时检测手术室中的边缘，（（4）合理选择分子治疗，以及（5）（5）在分子水平的饲养时间中监测治疗的反应。成像癌症的分子特征需要分子特异性对比剂，这些对比剂可以安全地用于体内以及成本效益的成像系统，以快速和非侵入性地对体内这些药物的摄取，分布和结合形象。射线照相成像模态（例如CT和MRI）虽然有助于描述晚期癌的深度，但不足以检测到小小的上皮内病变。光学成像是一种新的方式，可以实时，高分辨率的上皮组织成像。光学成像系统是便宜，健壮和便携式的。光学成像系统非常适合早期发现上皮内疾病并评估肿瘤边缘和对治疗的反应。该提案的目的是将光学成像系统和对比剂的开发与功能基因组学的进步相结合。我们将开发可以局部应用的分子特异性，光学活性对比剂。我们还将开发廉价，坚固且便携式成像系统，以监视目标生物标志物的三维轮廓。这些对比剂和成像系统将对许多类型的癌症具有广泛的适用性。在这里，我们将开发和测试子宫颈，口腔和肺部的剂和成像系统，该系统占全球肿瘤发病率和死亡率的20％以上。我们将测试这些对比剂和成像系统在动物模型中的安全性和功效，并提供数据以支持I和II期临床试验。该提案的目的是：（1）开发光学上的对比剂，以靶向肿瘤的四个分子特征，包括EGFR，MMP，MMP，端粒酶和Alpha V整合素；（2）确定将使用鼠尾草文库开发对比剂的有希望的新生物标志物，并使用组合方法确定新型对比剂的有希望的分子探针；（3）开发廉价的便携式光学系统，以实时形象肿瘤的形态和分子特征；（4）测试这些代理，递送制剂和成像系统的生命生物系统，以逐步提高复杂性。（5）我们的最终目的是整合这些研究以开发微型成像系统，当与此处开发的对比剂相结合时，可用于实时，分子检测肿瘤并在分子水平上监测病变是否对治疗有反应。