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）：这项工作的长期目标是为放射化学的基础研究和临床前应用做出贡献，以便更好地了解综合癌症中心的反应评估、分子和生理分析、细胞追踪和细胞表面靶向。所需的仪器将能够高效生产用于临床前研究的各种氟 18 标记放射性示踪剂。这些将利用莫菲特对成像研究的大量投资，其中最近包括在回旋加速器附近建造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，这些用户拥有 NIH 支持的现有项目，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。使用初期，18F-FAC； 18F-FHBG 和 18F-FMAU 将使用该系统生成，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，并且可以使用规格表。在 QA/QC 和仪器验收之后，将采用两种肽放射性标记途径：18F-NPFP 用于 RGD (Arg-Gly-Asp)；和 18F-SFB 来标记 pHLIP（pH 低插入肽）、MTI-101（内部开发用于结合 Hyd-1）和 MTI-T02（内部开发用于结合 TLR-2）。之后，计划探索 18F Nifene（结合烟碱 ¿4¿2 受体）、[18F] - FASu（Glu/Cys 转运蛋白 SLC7A11 的底物）和 18F-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费率。主要用户计划由 10 R01、1 U10、1 U54、1 P01 和 1 P50 拨款支持。该机构为该企业提供长期支持，除了设施的运营预算外，还将支付年度维护协议的费用。在资源允许的情况下，将支持更多的追踪器和开发项目，并将扩大支持和教育范围，以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，提高对疾病的个性化了解，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