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

描述（由申请人提供）：靶向分子显像剂的高通量设计、合成和体内评价。这是针对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。分子成像是一种在细胞和亚细胞水平上发生的体内分子过程的非侵入性定量可视化，正在成为个性化医疗的一项使能技术。靶向性分子显像剂的开发对该领域的发展至关重要。目前靶向分子显像剂快速发展的限制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显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的进步来筛选基于肽的文库，这些文库被设计为用于PET的靶向分子显像剂。我们组建了一个由Sutcliffe教授（放射化学家）、Cherry教授（PET物理学家）、Revzin教授（化学工程师）和Qi教授（物理学家/数学家）组成的多学科研究团队。根据《复苏法案》的宗旨，我们正在为学生和博士后申请资金，以支持该领域的培训，并为Dave Kukis和Jennifer Fung （CMGI的员工）提供技术支持，以确保保住工作。我们相信，通过专注于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大量和耗时的体外分析的需求。分子探针作为靶向成像生物标志物的发展进展将显著有助于促进个性化医疗，提高我们在许多疾病中检测、诊断、分期、监测和指导治疗反应以及确定预后的能力。

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.