New Chemical Methods for Molecular Imaging to Impact Clinical Care

描述(由申请人提供)：我们建议开发和使用一般和强大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。这一应用的创新依赖于概念新颖和最近开发的后期氟化化学。在这里，我们建议进一步发展这一新的化学技术，并将其用于合成PET示踪剂[18F]-F-DOPA，作为改善目前较低的放射性合成产率的原型应用，以及[18F]-PF-02341066，一种新近开发的抗肿瘤药物，它还不能通过标准的放射性合成方法进行放射性标记。PF-02341066的标记将使人们更好地了解该制剂在不同条件下的药代动力学和生物分布，以改善未来肺癌治疗患者的剂量和给药时机。基础科学的新进展将通过提供概念上的新的、快速的和通用的方法来合成目前无法获得的PET示踪剂，从而对医学成像产生革命性的影响。我们认为，这项提议的一个关键优势是由四个PI组成的联盟，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。认识到化学、分子PET成像和临床前应用之间相互依赖的早期合作有望引导创新化学的发展，使其立即用于PET成像应用，了解临床成像对人类健康的最终需求。 公共卫生相关性：正电子发射断层扫描(PET)是一种用于临床护理的强大的非侵入性成像技术。目前与PET相关的技术困难根源于其基本技术--放射性示踪剂合成，这需要新的通用和有效的化学方法。

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.