Commercialization of a Benchtop Radiosynthesizer for the Production of PET Probes

用于生产 PET 探针的台式放射合成仪的商业化

• 批准号: 8591614
• 负责人: Melissa Moore
• 金额: $ 59.84万
• 依托单位: SOFIE BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-25 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8591614
• 关键词: Address; Affect; Aliquot; Basic Science; Biochemical; Biological; Biological Markers; Biological Process; Biology; Brain; Brain Diseases; Brain imaging; Capital; Cells; Clinical; Clinical Research; Clinical Trials; Collection; Companions; Computer software; Critical Pathways; Cyclic GMP; Dependency; Detection; Development; Devices; Diagnostic; Disease; Dose; Drug Formulations; Electronics; Ensure; Environment; Equipment; Event; FDA approved; Fluorides; Freedom; Functional disorder; Future; Goals; Guidelines; High Pressure Liquid Chromatography; Human; Human Resources; Image; Incentives; Injection product; Intervention; Investments; Laboratories; Lead; Libraries; Liquid substance; Manuals; Measures; Medicine; Methods; Microfluidics; Miniaturization; Modeling; Monitor; Mus; Pathway interactions; Patient Care; Patients; Phase; Positron-Emission Tomography; Preparation; Price; Problem Solving; Process; Production; Public Health; Quality Control; Radioactivity; Radiochemistry; Radiolabeled; Reagent; Research; Research Infrastructure; Sampling; Scientist; Site; Solutions; Structure; System; Technology; Testing; Therapeutic; Time; Training; Treatment Efficacy; Validation; Vial device; base; biological systems; clinically relevant; commercialization; cost; design; empowered; glucose analog; graphical user interface; imaging modality; imaging probe; improved; interest; meetings; molecular imaging; novel; phase 1 study; point of care; prototype; public health relevance; radiation resistance; radiotracer; touchscreen; user-friendly

DESCRIPTION (provided by applicant): Positron Emission Tomography (PET) is a molecular imaging modality that utilizes radiolabeled molecules ("probes") to target and measure biological processes. Basic scientists can use the same probes to examine cells and mice as they do in patients to visualize and characterize the biology of disease, monitor its progression, and evaluate therapeutic efficacy. Although over 3,000 PET probes have been developed to help answer a variety of biological questions, including many specific to understanding the structure and function of the human brain, only the glucose analog [18F]FDG is routinely used for molecular imaging diagnostics in patient care today. This limitation exists because of the centralized approach to PET probe production necessitated by the high cost of infrastructure, specialized equipment, and skilled personnel required for synthesis. Overcoming these hindrances to PET probe development, optimization, and routine production is necessary to facilitate the entry of numerous other promising PET probes into clinical research and trials, and to select those with value as companion biomarkers. A decentralized approach to PET probe development is required to give scientists the freedom to determine what probes they want to use to best solve the problems of their interest. This goal can be achieved by building a benchtop, PC-controlled, microfluidic chip-based commercial device for the on-demand production of PET probes. Phase I of this project answered basic commercial feasibility questions about the underlying Electro- Wetting-On-Dielectric (EWOD) microfluidic chip technology. Phase II seeks to leverage previous research to address technological challenges inherent in creating a commercial microscale chip-based radiosynthesizer so the synthesis of diverse PET probes for clinical brain imaging can be performed in a simple and convenient manner at a low cost. Key objectives include development of an approach for large-scale manufacturing of low- cost, cGMP-compliant EWOD chips; design of an automated post-synthesis system, including HPLC fraction collection, formulation, and aliquoting of product for downstream quality control; development of a clinical version of the software platform and electronic control system; and development of proof-of-concept cGMP kits for the synthesis of a variety of probes for brain imaging. As an eventual product, a library of chips will be developed based on customer needs for different probes. Shifting to a point-of-research/point-of-care model is a transformational solution that removes the limitations imposed by the centralized model on probe production, cost, and diversity. By empowering scientists and clinicians to control the development and use of PET probes, they are able to focus on processes that they believe are most important.

描述（由申请人提供）：正电子发射断层扫描（PET）是一种分子成像模式，其利用放射性标记分子（“探针”）来靶向和测量生物过程。基础科学家可以使用相同的探针来检查细胞和小鼠，就像他们在患者中所做的那样，以可视化和表征疾病的生物学，监测其进展并评估治疗效果。尽管已经开发了超过3，000种PET探针来帮助回答各种生物学问题，包括许多特定于了解人脑结构和功能的问题，但目前只有葡萄糖类似物[18F]FDG常规用于患者护理中的分子成像诊断。这种限制的存在是因为PET探针生产的集中方法是合成所需的基础设施、专用设备和熟练人员的高成本所必需的。克服PET探针开发、优化和常规生产的这些障碍对于促进许多其他有前途的PET探针进入临床研究和试验，以及选择那些有价值的生物标志物是必要的。PET探头开发需要一种分散的方法，以使科学家能够自由决定他们想要使用什么探头来最好地解决他们感兴趣的问题。这一目标可以通过构建台式、PC控制、基于微流控芯片的商业设备来实现，用于按需生产PET探针。该项目的第一阶段回答了关于基础电润湿介质（EWOD）微流体芯片技术的基本商业可行性问题。第二阶段旨在利用先前的研究来解决创建基于商业微型芯片的放射性合成器所固有的技术挑战，以便以简单方便的方式以低成本合成用于临床脑成像的各种PET探针。主要目标包括开发用于大规模制造低成本、符合cGMP的EWOD芯片的方法;设计自动化合成后系统，包括HPLC级分收集、配制和用于下游质量控制的产品等分;开发软件平台和电子控制系统的临床版本;以及开发用于合成各种脑成像探针的cGMP概念验证试剂盒。作为最终产品，将根据客户对不同探头的需求开发芯片库。转向研究点/护理点模型是一种转型解决方案，它消除了集中式模型对探针生产、成本和多样性的限制。通过授权科学家和临床医生控制PET探头的开发和使用，他们能够专注于他们认为最重要的过程。