Center without Walls for Imaging Proteinopathies with PET (CW2IP2)

总体摘要 该申请描述了将创建一个新的中心，该中心将专注于正电子的发展 用于两种蛋白质病成像的发射断层扫描(PET)配体：1)α-突触核蛋白(ASYN) 对帕金森氏病和多系统萎缩的联核性疾病进行成像；以及，2)4R tau对 4R异常的额颞部变性和进行性核上性瘫痪的影像表现。这个名字 建议的中心之一是无壁PET蛋白病成像中心(CW2IP2)， 代表着宾夕法尼亚大学、 华盛顿大学圣彼得堡分校路易斯，匹兹堡大学，加州大学旧金山分校，耶鲁 大学，以及合同研究机构MedChem成像。本中心的组织机构 Without Wallels非常创新和独特，原因有很多：1)它的教职员工在 宾夕法尼亚大学在神经生物学领域享有国际声誉(V.Lee，K. )、神经病理学(J.Trojanowski)和结构生物学(E.J.Petersson；V.Moiseenkova-Bell) 蛋白质病进入PET放射性示踪剂领域--聚合型Asyn和4R显像剂的研制 2)它涉及宾夕法尼亚大学(RH Mach)、皮特(C.Mathis)、华盛顿大学的PET放射化学家的合作 (Z.Tu)和MedChem成像(N.Vasdev)，他们是中枢神经系统放射性示踪剂开发领域的专家； 3)它涉及临床研究人员的多地点协作，他们是使用PET的专家 研究中枢神经系统疾病(J Perlmutter(Wash U)，R.Carson(耶鲁大学)，G.Rabinovici(UCSF)，A.Siderowf (宾夕法尼亚))。这种多机构合作不仅符合RFA中描述的 创建一个没有围墙的中心，但有如此多样化的科学研究的个人参与 背景对于成功实现本论坛的科学目标至关重要。《少年派》 该中心的负责人是宾夕法尼亚大学布里顿·钱斯放射学教授罗伯特·H·马赫。该中心由 由一个行政核心和两个研究核心组成：药物化学和放射化学以及 临床核心。核心已经被组织成有一个整体的核心主任或联席主任， 以及参与核心活动的每个地点的一名现场主任。有两个研究项目 在这个U19中心，每个中心都专注于旨在由Medicinal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2/4R tau)。这 U19中心还将实施基础广泛的数据和资源共享计划，这将有利于 美国的临床研究人员，他们正在进行与科学任务相关的研究 NINDS和NIA。我们预计无壁中心的PET成像蛋白病 (CW2IP2)将导致基于NINDS和NIA的翻译研究在 并将促进我们对Asyn和4R tau在神经退行性变中的作用的了解。

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.