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High throughput design, synthesis and in vivo evaluation of targeted molecular im

靶向分子im的高通量设计、合成和体内评价

基本信息

批准号：
8047904
负责人：
JULIE L SUTCLIFFE
金额：
$ 352万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-30 至 2013-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8047904
关键词：
Address Affinity Animal Model Animals Area Automation Biological Biological Markers Biological Preservation Chemical Engineering Cherry - dietary Complex Data Data Collection Data Set Development Diagnosis Disease Evaluation Funding Genomics Goals Growth Half-Life Image Image Analysis Imagery Imaging technology In Vitro Libraries Medicine Methods Microfabrication Microfluidics Molecular Molecular Bank Molecular Probes Molecular Target Monitor Occupations Organ Peptides Performance Positron-Emission Tomography Postdoctoral Fellow Process Qi Radiolabeled Recovery Research Research Personnel Retrieval Screening procedure Staging Students Techniques Technology Therapeutic Time Training Support Translations base bench to bedside combinatorial combinatorial chemistry cost data acquisition design high throughput technology image reconstruction imaging Segmentation imaging probe improved in vivo molecular imaging multidisciplinary novel oncology outcome forecast pre-clinical process optimization professor radiotracer response therapeutic target treatment response

项目摘要

DESCRIPTION (provided by applicant): High throughput design, synthesis and in vivo evaluation of targeted molecular imaging agents. This is a 3-year proposal in response to the RFA-OD-10-005. This proposal addresses components of all 5 thematic areas with the closest association with the thematic area "Applying Genomics and other High throughput technologies". Molecular imaging, a noninvasive, quantitative visualization of in vivo molecular processes occurring at the cellular and sub cellular level is becoming an enabling technology for personalized medicine. Development of target specific molecular imaging agents is critical for the growth of this field. Current limitations for the rapid development of targeted molecular imaging agents include the complex design, synthesis and screening approaches for radiolabeled compounds, the short half-lives of the radiolabeled compounds, automation of the synthesis of radiolabeled compounds, rapid in vivo screening of the compounds and finally rapid automated analysis of the large data sets acquired. We are therefore proposing to address these limitations by developing a high-throughput platform that will streamline not only the in vitro selection but also the synthesis and in vivo evaluation of novel targeted molecular imaging agents. We will utilize the advances made in combinatorial chemistry, microfabrication, microfluidics and small animal imaging technologies to screen peptide based libraries designed as targeted molecular imaging agents for utilization with PET. We have assembled a multidisciplinary team of investigators Professors Sutcliffe (radiochemist), Cherry (PET physicist), Revzin (chemical engineer) and Qi (physicist/mathematician). In line with the purpose of the Recovery Act we are requesting funds for students and post doctoral fellows to support training in the field as well as technician support for Dave Kukis and Jennifer Fung (staff at CMGI) to enable job preservation. We believe that by focusing our efforts on high-throughput compound retrieval and in vivo screening our approach has the potential to minimize the need for extensive and time consuming in vitro analysis These advances in the development of molecular probes as targeted imaging biomarkers will significantly help to facilitate personalized medicine, improving our ability to detect, diagnose, stage, monitor and guide treatment response and determine prognosis in many diseases. PUBLIC HEALTH RELEVANCE: Molecular imaging is a noninvasive, quantitative visualization of in vivo molecular processes occurring at the cellular and sub cellular level that is becoming an enabling technology for personalized medicine. We are proposing to accelerate the development of target specific molecular imaging agents. These advances in the development of molecular imaging agents as targeted imaging biomarkers will significantly help to facilitate personalized medicine, improving our ability to detect, diagnose, stage, monitor and guide treatment response and determine prognosis in many diseases.

描述（由申请人提供）：靶向分子成像剂的高通量设计、合成和体内评估。这是响应 RFA-OD-10-005 的一项为期 3 年的提案。该提案涉及与“应用基因组学和其他高通量技术”主题领域最密切相关的所有 5 个主题领域的组成部分。分子成像是细胞和亚细胞水平上发生的体内分子过程的无创定量可视化，正在成为个性化医疗的一项支持技术。目标特异性分子成像剂的开发对于该领域的发展至关重要。目前快速开发靶向分子显像剂的局限性包括放射性标记化合物的复杂设计、合成和筛选方法、放射性标记化合物的半衰期短、放射性标记化合物合成的自动化、化合物的快速体内筛选以及最终对所获得的大数据集的快速自动化分析。因此，我们建议通过开发一个高通量平台来解决这些限制，该平台不仅可以简化体外选择，还可以简化新型靶向分子成像剂的合成和体内评估。我们将利用组合化学、微加工、微流体和小动物成像技术方面取得的进步来筛选基于肽的文库，这些文库设计为用于 PET 的靶向分子成像剂。我们组建了一个多学科研究小组，由 Sutcliffe 教授（放射化学家）、Cherry（PET 物理学家）、Revzin（化学工程师）和 Qi（物理学家/数学家）教授组成。根据《复苏法案》的目的，我们正在为学生和博士后研究员申请资金，以支持该领域的培训，并为 Dave Kukis 和 Jennifer Fung（CMGI 的工作人员）提供技术支持，以保住工作。我们相信，通过集中精力进行高通量化合物检索和体内筛选，我们的方法有可能最大限度地减少对广泛且耗时的体外分析的需求。作为靶向成像生物标志物的分子探针开发的这些进展将极大地有助于促进个性化医疗，提高我们检测、诊断、分期、监测和指导治疗反应以及确定许多疾病预后的能力。公共健康相关性：分子成像是一种对细胞和亚细胞水平上发生的体内分子过程进行无创、定量可视化的方法，正在成为个性化医疗的一项支持技术。我们建议加快目标特异性分子成像剂的开发。作为靶向成像生物标志物的分子成像剂的开发进展将极大地有助于促进个性化医疗，提高我们检测、诊断、分期、监测和指导治疗反应以及确定许多疾病预后的能力。