Molecular-Lab Radiopharmaceutical Synthesis System

分子实验室放射性药物合成系统

• 批准号: 8640558
• 负责人: Robert J. Gillies
• 金额: $ 24.24万
• 依托单位: H. LEE MOFFITT CANCER CTR & RES INST
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8640558
• 关键词: 2' -fluoro-5-methylarabinosyluracil; Agreement; Animals; Basic Science; Binding; Biological Markers; Budgets; Cancer Patient; Caring; Cell surface; Cells; Clinical Trials; Communities; Comprehensive Cancer Center; Core Facility; Cyclotrons; Disease; Education; Fluorine; Grant; Housing; Image; Institution; Investments; Knowledge; Label; Laboratories; Maintenance; Malignant Neoplasms; Molecular; Monitor; Oxygenases; Peptides; Physiological; Production; RGD (sequence); Radiochemistry; Radiolabeled; Radiopharmaceuticals; Research; Resources; Robotics; Route; Services; System; TNFRSF5 gene; Tracer; United States National Institutes of Health; Work; clinical application; cost; improved; indoleamine; instrument; interest; new therapeutic target; pre-clinical; programs; radiotracer; receptor; response; treatment effect

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.

描述（由申请人提供）：本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，以更好地了解综合癌症中心的反应评估，分子和生理分析，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。这将充分利用莫菲特在成像研究方面的大量投资，其中包括最近在回旋加速器附近建立一个研究放射化学实验室。优先分配给8个主要用户最感兴趣的示踪剂，这些示踪剂与现有的NIH支持的研究癌症中新的治疗靶点或治疗反应生物标志物的项目有关。在使用初期，18F-FAC；该系统将生成18F-FHBG和18F-FMAU，因为这些放射性示踪剂先前已在模块化实验室系统上合成，并且可以获得规格表。在QA/QC和仪器签字之后，将采用两条多肽放射性标记路线：用于RGD的18F-NPFP (Arg-Gly-Asp)；和18F-SFB分别标记pHLIP （pH低插入肽）、MTI-101（自行开发结合Hyd-1）、MTI-T02（自行开发结合TLR-2）。在此之后，计划继续探索18F- Nifene（结合烟碱受体），[18F] - FASu （Glu/Cys转运体SLC7A11的底物）和18F- cmd（吲哚胺二加氧酶，IDO的底物）。由于这些示踪剂的种类和数量要在有限的空间内制造，因此需要一个占地面积小的机器人合成系统。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。主要用户程序支持10个R01、1个U10、1个U54、1个P01和1个P50。研究所为这项事业提供长期支助，除了设施的业务预算外，还将支付年度维修协议的费用。在资源允许的情况下，将支持更多的追踪者和开发项目，支持和教育将扩大，使更广泛的研究和护理界受益。这些示踪剂将使癌症患者受益，改善对其疾病的个性化了解，并改善对治疗效果的监测和预测。

项目成果

Evaluation of radiofluorinated carboximidamides as potential IDO-targeted PET tracers for cancer imaging.

评估放射性氟羧酰胺作为癌症成像的潜在易于染料的宠物示踪剂。

• DOI: 10.18632/oncotarget.14898
• 发表时间: 2017-07-18
• 期刊: Oncotarget
• 作者: Huang X;Pan Z;Doligalski ML;Xiao X;Ruiz E;Budzevich MM;Tian H
• 通讯作者: Tian H