An integrated radiopharmaceutical synthesis system

描述(由申请人提供)：该提案的目标是在加州大学戴维斯分校医学中心安装仪器，用于生产非商用的、适合人类使用的放射性标记显像剂。加州大学戴维斯分校医疗中心在其位于萨克拉门托的主医院园区完成了良好制造规范(GMP)实验室的建设。这个GMP实验室是一个多用途、6个制造套件、10,000级的设施。我们建议将商业放射性药物合成系统用于生产PET放射性药物，该系统的设计完全带有屏蔽外壳，使放射性药物的生产完全符合GMP。该合成系统允许通过亲核取代反应自动生产标记有正电子发射体18F的PET放射性药物。完整的集成系统包括符合FDA GMP法规和USP 797的所有必要文件。由于NIH路线图呼吁重视翻译研究，并将分子成像确定为优先事项，加州大学戴维斯分校提议在动物模型中建立一座从功能和分子成像到人类的桥梁。显然，目前在人类受试者的临床和研究分子成像方面仍然存在着显著的差距。这一差距与缺乏用于临床和研究人类正电子发射计算机断层扫描的非商用分子成像放射性药物有关。将该系统安装到我们最先进的GMP设施中将是为促进弥合这一差距而采取的第一步。该系统将用于支持从癌症到细胞疗法的临床研究，还将用于对加州大学戴维斯分校正在开发的一系列新诊断和治疗药物进行首次人体研究。分子成像领域寻求发现新的方法来对体内特定的生物靶点和途径进行成像，最终目标是提供针对患者的、基于分子的诊断、预后和治疗。加州大学戴维斯分校的教师在分子靶向显像剂的设计方面拥有专业知识，目前正在动物模型中进行研究，在翻译阶段有几个线索。拟议的集成系统将允许我们合成既符合FDA GMP又符合USP 797的诊断显像剂的既有的和新型的PET放射性药物，用于人体成像研究。

DESCRIPTION (provided by applicant): The goal of this proposal is to install instrumentation for the production of non-commercially available radiolabeled imaging agents suitable for human use at the UC Davis Medical Center. UC Davis Medical Center is completing a Good Manufacturing Practice (GMP) laboratory at its main hospital campus in Sacramento. This GMP laboratory is a multi-use, 6 manufacturing suite, Class 10,000 facility. We propose to incorporate a commercial radiopharmaceutical synthesis system for the production of PET radiopharmaceuticals that has been designed complete with shielding enclosures allowing the production of radiopharmaceuticals to take place under full GMP compliance. The synthesis system allows the automated production of PET radiopharmaceuticals labeled with the positron emitter 18F via nucleophilic substitution reactions. The complete integrated system includes all necessary documentation for compliance with FDA GMP regulations as well as USP 797. As the NIH roadmap calls for an emphasis on translational research and has identified molecular imaging as a priority, UC Davis is proposing to build a bridge from functional and molecular imaging in animal models to humans. It is clear that currently a significant gap persists with regard to clinical and research molecular imaging in human subjects. This gap relates to the lack of access to non-commercially available molecular imaging radiopharmaceuticals for clinical and research human PET. Installation of this system into our state-of-the-art GMP facility will be the first step taken to facilitate bridging this gap. The system will be used to support clinical research ranging from cancer to cellular therapies, and will also be used to perform first in man studies of a range of new diagnostic and therapeutic agents under development by UC Davis faculty. The field of molecular imaging seeks to discover new approaches to imaging specific biologic targets and pathways in vivo, with the ultimate goal of providing patient-specific and molecularly-based diagnosis, prognosis and therapy. The faculty at UC Davis have expertise in the design of molecularly-targeted imaging agents that are currently under investigation in animal models with several leads at the translational stage. The proposed integrated system will allow us to synthesize both established and novel PET radiopharmaceuticals as diagnostic imaging agents complying with both FDA GMP as well as USP 797 for use in human imaging studies.