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: 8075274
• 负责人: Jacob M. Hooker
• 金额: $ 59.13万
• 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 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8075274
• 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; 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. PUBLIC HEALTH RELEVANCE: Positron-emission tomography (PET) is a powerful non-invasive imaging technology used in clinical care. The current technical difficulties associated with PET are rooted in its underlying technology, radiotracer synthesis, which requires new general and efficient chemical methods.

描述（由申请人提供）：我们提出了一般和强大的后期荧光化学的开发和使用，用于合成正电子发射断层扫描（PET）示踪剂用于分子成像。该应用程序的创新依赖于概念上的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型的化学技术，并将其用于宠物示踪剂[18F] -F-DOPA的合成，作为一种原型应用，以提高当前低的放射性合成产量，以及[18F] -PF-02341066，最近开发的抗神经脱萝卜剂，无法通过标准的辐射方法进行辐射方法。 PF-02341066的标签将使对药代动力学的药代动力学和生物分布在各种条件下，以改善接受肺癌治疗的患者的未来给药和时机。基础科学的新进步将对医学成像产生变革性的影响，通过在概念上提供新的，快速和一般的方法来综合当前不可用的宠物示踪剂。我们认为，该提案的关键优势是由四个PI的财团组成，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家知识。预计化学，分子PET成像和临床前应用之间的相互依存的早期合作有望将创新化学的发展引导到其在PET成像中的立即用于PET成像，这是由于临床对人类健康的最终需求所示。 公共卫生相关性：正电子发射断层扫描（PET）是一种在临床护理中使用的强大的非侵入性成像技术。当前与PET相关的技术困难植根于其基础技术，Radiotracer合成，这需要新的通用和有效的化学方法。