Commercialization of a Benchtop Radiosynthesizer for the Production of PET Probes

描述（由申请人提供）：正电子发射断层扫描（PET）是一种分子成像方式，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，就像他们在病人身上做的那样，以观察和描述疾病的生物学特征，监测其进展，并评估治疗效果。尽管已经开发了3000多个PET探针来帮助回答各种生物学问题，包括许多特定于理解人类大脑的结构和功能的问题，但目前只有葡萄糖类似物[18F]FDG被常规用于患者护理中的分子成像诊断。这种限制的存在是由于PET探针生产的集中式方法需要高成本的基础设施、专用设备和合成所需的熟练人员。克服这些阻碍PET探针开发、优化和常规生产的障碍是必要的，以促进许多其他有前途的PET探针进入临床研究和试验，并选择那些有价值的伴随生物标志物。需要一种分散的PET探针开发方法，使科学家能够自由决定他们想要使用哪种探针来最好地解决他们感兴趣的问题。这一目标可以通过建立一个台式、pc控制、基于微流控芯片的商用设备来实现，用于按需生产PET探针。该项目的第一阶段回答了有关电介质电润湿（EWOD）微流控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商业微尺度芯片放射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。主要目标包括开发大规模生产低成本、符合cgmp的EWOD芯片的方法；设计一个自动化的合成后系统，包括高效液相色谱收集、配方和下游质量控制产品的aliquote；开发临床版软件平台及电控系统；以及开发用于合成各种脑成像探针的概念验证cGMP试剂盒。作为最终产品，将根据客户对不同探头的需求开发一个芯片库。转向研究点/护理点模型是一种变革性的解决方案，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探针的开发和使用，他们能够专注于他们认为最重要的过程。

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.