Metal-Mediated C-H Radiofluorination for Rapid Access to PET Imaging Agents

金属介导的 C-H 放射性氟化用于快速获得 PET 成像剂

基本信息

批准号：
10615600
负责人：
Jay Samuel Wright
金额：
$ 7.81万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10615600
关键词：
Acids Adoption Agrochemicals Amidines Amines Antimalarials Biotechnology Chemistry Chloroquine Clinical Clinical Trials Copper Data Detection Development Diagnostic Discipline Disease Disease Progression Drug Costs Drug Industry Drug Targeting Elements Environment Financial cost Fluorides Fluorine Goals Grant Healthcare Human Hydrogen Bonding Image Image Enhancement Imaging Techniques Institution Interdisciplinary Study Knowledge Label Laboratories Libraries Ligands Manuals Marketing Mediating Medicine Mentors Metals Methodology Methods Michigan Mission Modeling Monitor National Institute of Biomedical Imaging and Bioengineering Organometallic Chemistry Oxides Periodicals Pharmaceutical Preparations Pharmacologic Substance Pharmacology Phase Population Positioning Attribute Positron-Emission Tomography Preparation Procedures Process Production Property Protocols documentation Quinine Radio Radioactive Radiochemistry Radioisotopes Radiolabeled Radiology Specialty Radiopharmaceuticals Rationalization Reaction Research Research Design Research Proposals Role Salts Scanning Silver Silver Compounds Sodium Chloride Tracer Training Translating Universities Validation Vitamin B6 analog bioactive scaffold bioimaging cancer imaging career career development clinical translation cost design disease diagnostic disorder prevention drug development drug discovery experience experimental study imaging agent imaging modality imaging study improved innovation invention neuroimaging novel novel therapeutics nuclear imaging oxidation patient population pharmacologic protocol development quinoline scaffold screening skills stable isotope translational study

项目摘要

Project Summary/Abstract Fluorine is an essential constituent of many commercial molecules, including (radio)pharmaceuticals, agrochemicals, and functional materials. Fluorine-19 (stable isotope) is routinely introduced into aromatic pharmaceuticals in order to modulate pharmacological properties. Many positron emission tomography aromatic (PET) imaging agents are labeled with fluorine-18 (radioactive isotope) for studying and monitoring disease, as well as evaluating drug-target engagements and enriching clinical trials. Considerable progress has been made in the development of aromatic fluorine-18 imaging agents for these applications, although more robust radiosyntheses are required to support and expedite tracer discovery and meet the increasing demand for radiopharmaceuticals from the healthcare and pharmaceutical industries. The primary aim of this project is to overcome challenges associated with radiofluorination through the invention of radiosynthetic methods that support the design of aromatic PET imaging agents. Specifically, the central claim is that radiofluorinated organic molecules can be accessed by designing silver- and copper-containing species competent in C-H radiofluorination. Copper is an abundant and inexpensive element that has previously been shown to (radio)fluorinate aromatic C-H bonds, albeit with a limited scope. Silver resides in the same periodic group as copper and preliminary data suggests that it can induce C-H radiofluorination transformations. To achieve these goals, the proposal is divided into three aims: Aim 1 is to use fluorine-18 labeled silver compounds for the radiofluorination of organic molecules. Aim 2 is to utilize this method for the automated radiosynthesis of fluorine- 18 labeled bioactive molecules Aim 3 is to develop new copper-mediated C-H functionalization methodologies for the direct, automated fluorine-18 labeling of aromatic bioactive molecules. Ultimately, enhancement of this imaging modality as described in this grant is expected to fundamentally alter the current radiosynthetic paradigm and expedite aromatic radiofluorination, providing new and rapid access to fluorine-18 labeled pharmaceuticals used in PET. Importantly, developments in PET biotechnology are continually being used to fundamentally improve the detection, treatment, and prevention of disease, consistent with the mission of NIBIB. This grant builds on the ongoing multidisciplinary collaboration between Prof Peter J. H. Scott (Department of Radiology) and Prof Melanie S. Sanford (Department of Chemistry), which focuses on the development of radiosynthetic methods at the University of Michigan. The facilities and faulty/staff expertise offered in these laboratories provide an outstanding research environment that will facilitate the candidate's acquisition of further skills necessary for gaining an academic position at a US institution, consistent with his long-term career goal. In particular, this project will provide new opportunities to merge radiochemistry and organometallic chemistry, which will serve the candidate's career development toward a professorship in chemistry with a focus on C-H radiolabeling for PET applications.