Molecular-Lab Radiopharmaceutical Synthesis System

描述（由申请人提供）：这项工作的长期目标是促进放射化学的基础研究和临床前应用，以便更好地了解综合癌症中心的反应评估，分子和生理学分析，细胞跟踪和细胞表面靶向。所要求的仪器将允许有效地生产各种氟-18标记的放射性示踪剂，用于临床前研究。这些将利用莫菲特已经大量投资于成像研究，其中最近包括在回旋加速器附近建立一个研究放射化学实验室。优先级分配给8个主要用户最感兴趣的示踪剂，这些用户具有现有的NIH支持的项目，这些项目研究癌症中的新治疗靶点或治疗反应生物标志物。在使用的初始阶段，将使用该系统生成18F-FAC、18F-FHBG和18F-FMAU，因为这些放射性示踪剂之前已在模块化实验室系统上合成，并且规格表可用。在QA/QC和仪器签收后，将采用两种肽放射性标记途径：18F-NPFP用于RGD（Arg-Gly-Asp）; 18F-SFB用于标记pHLIP（pH低插入肽）、MTI-101（内部开发以结合Hyd-1）和MTI-T02（内部开发以结合TLR-2）。在此之后，计划继续探索18 F Nifene（结合尼古丁受体），[18 F] - FASu（Glu/Cys转运蛋白SLC 7A 11的底物）和18 F-CMD（吲哚胺双加氧酶，IDO的底物）。由于要在有限的空间内制造这些示踪剂的种类和数量，因此需要小占地面积的机器人合成系统。该仪器将作为小动物成像核心设施内的共享服务进行管理，该设施将负责确定充电率。主要用户方案得到10个R 01、1个U10、1个U 54、1个P01和1个P50赠款的支持。该机构为该企业提供长期支持，除设施的业务预算外，还将支付年度维护协议的费用。在资源允许的情况下，将支持额外的示踪剂和开发计划，并将扩大支持和教育，使更广泛的研究和护理社区受益。这些示踪剂将使癌症患者受益，改善其疾病的个性化知识，并改善对治疗效果的监测和预测。

DESCRIPTION (provided by applicant): The long-term objective of this work is to contribute to basic research and pre-clinical applications of radiochemistry for better understanding of response assessment, molecular and physiological profiling, cell tracking and cell surface targeting in a comprehensive cancer center. The requested instrument will allow the efficient production of an assortment of fluorine-18 labeled radiotracers for pre-clinical investigations. These will leverage an already substantial investment of the Moffitt into imaging research, which has recently included the build out of a research radiochemistry laboratory adjacent to the cyclotron. Priority is assigned to tracers of highest interest to 8 major users with existing NIH supported programs that investigate novel therapeutic targets, or therapy response biomarkers in cancer. In the initial period of use, 18F-FAC; 18F-FHBG and 18F-FMAU will be generated with this system, as these radiotracers have previously been synthesized on the Modular Lab system and spec sheets are available. Following QA/QC and signoff of the instrument, two routes for peptide radiolabeling will be pursued: 18F-NPFP for RGD (Arg-Gly-Asp); and 18F-SFB to label pHLIP (pH low insertion peptide), MTI-101 (developed in house to bind Hyd-1), and MTI-T02 (developed in house to bind TLR-2). After these, there are plans to pursue 18F Nifene (binds Nicotinic ¿4¿2 receptor), [18F] - FASu (substrate for Glu/Cys transporter SLC7A11) and 18F-CMD (substrate for indoleamine di-oxygenase, IDO) will be explored. Because of the variety and number of these tracers to be made within limited space, a small footprint robotic synthesis system is needed. The instrument will be managed as a shared service within the Small Animal Imaging core facility, which will be responsible for establishing recharge rates. Major user programs are supported by 10 R01, 1 U10, 1 U54, 1 P01 and 1 P50 grant. Long term support for this enterprise is provided by the Institution, which will cover the costs of the annual maintenance agreement apart from the facility's operating budget. Additional tracers, and developing programs will be supported as resources permit, and support and education will be extended to benefit the wider research and care community. These tracers will benefit cancer patients with improved, personalized knowledge of their disease, and from improved monitoring and prediction of treatment effects.