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Fluoride-Mediated Desilylative Radiosynthesis of 11C-Labeled PET Tracers

氟化物介导的 11C 标记 PET 示踪剂的脱甲硅烷基放射合成

基本信息

批准号：
10442985
负责人：
Wenchao Qu
金额：
$ 35.58万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
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 2026-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10442985
关键词：
Acetic Acids Address Affinity Aldehydes Amides Anions Basic Science Biochemical Biological Carbon Carbon Dioxide Carboxylic Acids Cardiovascular system Catalysis Chemicals Chemistry Clinical Clinical Research Cyclotrons Development Disease Electrons Esters Event Fatty Acids Fluorides Gases Goals Half-Life Hybrids Imaging Device Imaging Techniques In Situ Intervention Investigation Label Lead Longitudinal Studies Low Dose Radiation Mediating Metabolism Metals Methodology Methods Methylation Modality Molecular Neurologic Nitrogen Nuclear Organism Oxygen Palmitic Acids Pharmaceutical Preparations Pharmacology Positioning Attribute Positron Positron-Emission Tomography Production Property Pyruvic Acid Radio Radiochemistry Radioisotopes Radiolabeled Reaction Reagent Reporting Research Research Personnel Scanning Skeleton Solvents Source Structure Succinic Acids Sulfonamides Sulfur Temperature Thermodynamics Tracer Translating Vorozole base biological systems carboxylation chemical property clinical diagnostics enzyme substrate functional group in vivo interest molecular imaging novel novel strategies radiochemical radiotracer receptor binding screening

项目摘要

PROJECT SUMMARY Positron emission tomography (PET) is a highly sensitive molecular imaging technique used for studying biological systems in vivo, as well as for clinical diagnostic purposes. The ubiquitous presence of carbon in most organic molecules makes carbon-11 an attractive and important positron-emitting radionuclide for labeling molecules of biological interest. Because 11C has the same chemical properties as 12C, 11C is especially useful for rapid exploration of molecules with well-characterized biological and pharmacological properties (i.e., metabolism, receptor binding affinity, enzyme substrate affinity, etc.). In addition, the short half- life of 11C (20.4 min) facilitates the possibility of multiple studies on the same subject in a single day due to the low radiation dose and absence of overlapping activity between scans. This opens up the possibility for longitudinal studies and studies involving an intervention, making it particularly desirable for basic and clinical research investigations. The lack of methods to introduce and incorperate11C into organic molecules conveniently and quickly limits the utility of this radioisotope. So far, the main criteria for successful synthesis of 11C-lableled PET tracers is a rapid, robust and practical radiolabeling method that yields the desired tracer with high radiochemical purity, chemical purity, and/or high molar activity. This is especially a challenge when [11C]CO2 is used as radiosynthon for synthesis of desired PET tracers. In this proposal, we will develop methods to address this issue. Our three Specific Aims are: 1). develop a fluoride-mediated desilylation (FMDS) 11C-labeling methodology to directly incorporate [11C]CO2 into skeleton of molecules with diversified structures. It is expected that this novel approach will provide facile and rapid access to 11C-labeled compounds with carbon-11 attached at various hybridized carbons (sp, sp 2 and sp3) with broad functional group tolerance; 2). Further extend FMDS 11C-labeling methodology to other accessible 11C-electrophiles (such as [11C]CH3I/[11C]CH3OTf). Our goal is to develop a new 11C-methylation method, which can serve as a complementary approach for synthesis of various 11C-labeled PET tracers; 3). Utilize FMDS 11C-labeling to solve some long-standing problems in radiotracer chemistry research by developing facile and practical labeling methods for radiotracers of high clinical interest where regular production is very difficult using currently reported methods, such as [11C]pyruvic acid, [11C]succinic acid, [11C]PHNO, [11C]vorozole. This newly developed FMDS 11C-labeling methodology may lead a brand new direction in radiotracer chemistry and open multiple avenues for developing novel and practical radiolabeling methodologies.

项目总结