An integrated radiopharmaceutical synthesis system

描述（由申请人提供）：本提案的目标是为加州大学戴维斯分校医学中心适合人类使用的非市售放射性标记显像剂的生产安装仪器。加州大学戴维斯分校医学中心正在萨克拉门托的主医院校区完成一个良好生产规范（GMP）实验室。本GMP实验室是一个多用途，6个生产套房，10000级设施。我们建议合并一个商业放射性药物合成系统，用于生产PET放射性药物，该系统已被设计成完整的屏蔽罩，允许放射性药物的生产完全符合GMP要求。该合成系统允许通过亲核取代反应自动生产带有正电子发射器18F标记的PET放射性药物。完整的集成系统包括符合FDA GMP法规以及USP 797的所有必要文件。由于NIH的路线图要求强调转化研究，并将分子成像确定为优先事项，加州大学戴维斯分校提议建立从动物模型到人类的功能和分子成像的桥梁。很明显，目前在临床和研究人类分子成像方面仍然存在重大差距。这一差距与缺乏用于临床和研究人类PET的非市售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，将是促进弥合这一差距的第一步。该系统将用于支持从癌症到细胞治疗的临床研究，也将用于加州大学戴维斯分校教师正在开发的一系列新的诊断和治疗药物的首次人体研究。分子成像领域寻求发现新的方法来成像体内特定的生物靶点和途径，最终目标是提供患者特异性和基于分子的诊断、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具有专业知识，目前正在动物模型中进行研究，并处于转化阶段。拟议的集成系统将允许我们合成已建立的和新的PET放射性药物作为诊断显像剂，符合FDA GMP和USP 797，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.