Center without Walls for Imaging Proteinopathies with PET (CW2IP2)

总体摘要 申请书描述了一个新中心的创建，该中心将专注于Positron的发展 用于成像两种蛋白质病的发射断层扫描（PET）配体： 对突触核蛋白病帕金森病和多系统萎缩进行成像;以及，2）4 R tau用于 对4 R tau蛋白病额颞变性和进行性核上性麻痹进行成像。名称 拟议中心的一部分是PET蛋白质病变成像无墙中心（CW 2 IP 2）， 代表了宾夕法尼亚大学， 华盛顿圣路易斯大学、匹兹堡大学、加州大学旧金山弗朗西斯科、耶鲁大学 大学和合同研究组织MedChem Imaging。本中心的组织 无墙是高度创新和独特的各种原因：1）它从事教师在 宾夕法尼亚大学在神经生物学领域享有国际声誉（V. Lee，K. Luk）、神经病理学（J. Trojanowski）和结构生物学（E. J. Petersson; V. Moiseenkova-Bell）。 PET放射性示踪剂开发领域的蛋白质病，用于成像聚集的Asyn和4 R 2）它涉及宾夕法尼亚大学（RH马赫），皮特（C。马西斯），华盛顿大学 （Z. Tu）和MedChem Imaging（N. Vasdev），他们是CNS放射性示踪剂开发领域的专家; 以及3）它涉及临床研究人员的多地点合作，这些研究人员是PET使用方面的专家， 研究CNS疾病（J Perlmutter（Wash U），R.卡森（耶鲁），G. Rabinovici（UCSF），A.西德罗夫 （Penn））。这种多机构合作不仅符合RFA中所述的标准， 创建一个没有围墙的中心，但拥有如此多样化科学知识的个人的参与 背景对于成功实现RFA的科学目标至关重要。的PI 该中心是罗伯特H。马赫说，宾夕法尼亚大学的布里顿机会放射学教授。该中心由 一个行政核心和两个研究核心：药物化学和放射化学和 临床核心。核心的组织方式是，有一名总的核心主任或联合主任， 以及参与核心活动的每个研究中心的研究中心主任。有两个研究项目 在这个U19中心，每一个都专注于针对由医药公司开发的验证探针的研究。 蛋白质病的化学和放射化学核心（项目1/Asyn和项目2/4 R tau）。这 U19中心还将实施一项基础广泛的数据和资源共享计划， 在美国进行与科学使命相关研究的临床研究者 NINDS和NIA。我们预计，该中心没有墙成像蛋白质病变与PET （CW 2 IP 2）将导致NINDS和NIA为基础的翻译研究的显着扩展， 国家水平，并将推进我们对Asyn和4 R tau在神经变性中的作用的认识。

OVERALL ABSTRACT The application describes the creation of a new center that will focus on the development of Positron Emission Tomography (PET) ligands for imaging two proteinopathies: 1) alpha synuclein (Asyn) for imaging the synucleinopathies Parkinson's disease and multiple system atrophy; and, 2) 4R tau for imaging the 4R tauopathies frontotemporal degeneration and progressive supranuclear palsy. The name of the proposed center is the Center without Walls for Imaging Proteinopathies with PET (CW2IP2), and represents a multi-institutional collaborative effort between the University of Pennsylvania, Washington University-St. Louis, University of Pittsburgh, University of California-San Francisco, Yale University, and the contract research organization, MedChem Imaging. The organization of this Center without Walls is highly innovative and unique for a variety of reasons: 1) it engages faculty members at the University of Pennsylvania having an international reputation in the fields of neurobiology (V. Lee, K. Luk), neuropathology (J. Trojanowski), and structural biology (E.J. Petersson; V. Moiseenkova-Bell) of the proteinopathies into the field of PET radiotracer development for imaging aggregated Asyn and 4R tau; 2) it involves the collaboration of PET radiochemists at Penn (RH Mach), Pitt (C. Mathis), Wash U (Z. Tu) and MedChem Imaging (N. Vasdev) who are experts in the field of CNS radiotracer development; and 3) it involves the multi-site collaboration of clinical investigators who are experts in the use of PET to study CNS disorders (J Perlmutter (Wash U), R. Carson (Yale), G. Rabinovici (UCSF), A. Siderowf (Penn)). This multi-institutional collaboration not only meets the criteria described in the RFA for the Creation of a Center without Walls, but the participation of individuals having such diverse scientific backgrounds will be essential for successfully accomplishing the scientific objectives of this RFA. The PI of the Center is Robert H. Mach, the Britton Chance Professor of Radiology at Penn. The center consists of an Administrative Core and two research cores: Medicinal Chemistry and Radiochemistry and the Clinical Core. The cores have been organized such that there is an overall Core Director or Co-Director, and a site Director at each of the sites participating in the Core activities. There are two research projects in this U19 Center, each focused on studies aimed at validation probes developed by the Medicinal Chemistry and Radiochemistry Core for a proteinopathy (Project 1/Asyn and Project 2/4R tau). This U19 Center will also implement a broad-based Data and Resource Sharing Plan that will be of benefit to clinical investigators in the US who are conducting research relevant to the scientific mission of the NINDS and NIA. We anticipate that the Center without Walls for Imaging Proteinopathies with PET (CW2IP2) will lead to a significant expansion of NINDS- and NIA-based translational research at the national level, and will advance our knowledge on the role of Asyn and 4R tau in neurodegeneration.