New Chemical Methods for Molecular Imaging to Impact Clinical Care

分子成像的新化学方法影响临床护理

• 批准号: 8661770
• 负责人: Jacob M. Hooker
• 金额: $ 51.86万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-15 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8661770
• 关键词: Basic Science; Biodistribution; Carbon; Cell Nucleus; Chemicals; Chemistry; Clinical; Collaborations; Complex; Development; Dose; Drug Kinetics; Fluorides; Fluorine; Future; Glucose; Goals; Half-Life; Health; Human; Image; Imaging technology; Injection of therapeutic agent; Isotopes; Knowledge; Label; Malignant neoplasm of lung; Mediating; Medical Imaging; Medical Research; Methodology; Methods; Molecular; Palladium; Patient Care; Patients; Plant Roots; Positron-Emission Tomography; Radiochemistry; Radiolabeled; Reaction; Reaction Time; Research; Rodent; Role; Series; Silver; Staging; Synthesis Chemistry; Technology; Time; Tracer; Validation; cancer diagnosis; chemical reaction; chemical synthesis; clinical care; functional group; imaging probe; improved; in vivo; inhibitor/antagonist; innovation; interest; meetings; molecular imaging; neoplastic; non-invasive imaging; novel; pre-clinical; prototype; radiochemical; radiotracer; reaction rate (chemical); small molecule; tool

DESCRIPTION (provided by applicant): We propose the development and use of general and robust late-stage fluorination chemistry for the synthesis of positron emission tomography (PET) tracers for molecular imaging. The innovation of this application relies on conceptually-novel and recently-developed late-stage fluorination chemistry. Here we propose to develop this novel chemical technology further and use it for the synthesis of the PET tracers [18F]-F-DOPA, as a prototype application to improve currently low radiosynthesis yields, and [18F]-PF-02341066, a recently developed anti-neoplastic agent, which has not been amenable to radiolabeling through standard radiosynthetic methods. The labeling of PF-02341066 will allow an increased understanding of the pharmacokinetics and biodistribution of the agent under various conditions, to improve future dosing and timing of administration in patients undergoing therapy for lung cancer. The new advancement in basic science will have a transformative impact on medical imaging by providing conceptually new, rapid, and general approach to the synthesis of currently unavailable PET tracers. We believe that a key strength of this proposal is the assembly of a consortium of four PIs that unifies expert knowledge in chemistry, radiochemistry, imaging probe development, and molecular imaging. Early collaboration that acknowledges the interdependence between chemistry, molecular PET imaging, and preclinical applications is expected to direct the development of innovative chemistry toward its immediate use in applications for PET imaging, informed by the ultimate need in clinical imaging for human health.

描述（由申请人提供）：我们建议开发和使用通用且稳健的后期氟化化学来合成用于分子成像的正电子发射断层扫描（PET）示踪剂。该应用的创新依赖于概念新颖且最近开发的后期氟化化学。在这里，我们建议进一步开发这种新颖的化学技术，并将其用于合成 PET 示踪剂 [18F]-F-DOPA，作为提高目前较低的放射合成产率的原型应用，以及最近的 [18F]-PF-02341066开发了抗肿瘤剂，该剂不适合通过标准放射合成方法进行放射性标记。 PF-02341066 的标签将有助于加深对该药物在各种条件下的药代动力学和生物分布的了解，以改善接受肺癌治疗的患者未来的剂量和给药时间。基础科学的新进展将为目前无法使用的 PET 示踪剂的合成提供概念上新颖、快速且通用的方法，从而对医学成像产生变革性影响。我们认为，该提案的一个关键优势是由四个 PI 组成的联盟的集合，该联盟统一了化学、放射化学、成像探针开发和分子成像方面的专业知识。早期合作承认化学、分子 PET 成像和临床前应用之间的相互依赖性，预计将指导创新化学的发展，使其直接用于 PET 成像应用，以满足人类健康临床成像的最终需求。