PF-L-DOPA: a MRI tool for developmental neurobiology

PF-L-DOPA：发育神经生物学的 MRI 工具

• 批准号: 6914140
• 负责人: SHERRY DINGMAN
• 金额: $ 4.3万
• 依托单位: MARIST COLLEGE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6914140
• 关键词: Insecta; alternatives to animals in research; behavior test; bioimaging /biomedical imaging; biological models; brain; brain imaging /visualization /scanning; chick embryo; crayfish; developmental neurobiology; drug design /synthesis /production; drug screening /evaluation; fluorescent dye /probe; high performance liquid chromatography; histogenesis; immunologic assay /test; isomer; levodopa; magnetic resonance imaging; method development; neuropharmacology; neurotransmitters; nuclear magnetic resonance spectroscopy; pharmacokinetics; self medication

DESCRIPTION (provided by applicant): Neurobiological and genetic factors certainly influence drug abuse and addiction. Understanding how genetic factors interact with environmental factors during brain development is crucial to unraveling the etiology of addiction. The long-term objective of this research project is to develop powerful new tools for investigating how early environmental factors, such as perinatal stress or exposure to drugs, contribute to creating individual differences in biological susceptibility to addiction and other disorders. Ultimately the project aims to use perfluorinated neurotransmitters as imaging agents for studying the epigenesis of neural pathways with magnetic resonance imaging (MRI). This project will investigate perfluorinated L-DOPA and determine the best isomer of 19F-L-DOPA for use in vivo. The project will include developing imaging protocols for detecting the compound at low concentrations, project proposed will include: (1) synthesis, isolation, characterization and purification of perfluoro-tagged isomers of L-DOPA (2) in vitro enzymatic assay characterization of compounds (3) immunoassay screen to characterize the uptake and bioavailability of the novel compounds in vivo, using in ova Gallus domestics (4) devising of MRI protocols for use of the best perfluoroalkyl-tagged isomers. The usefulness of MRI as a research tool for studying the brain and its development would be vastly enhanced if it were possible to directly image specific neuropathways and events related to the synthesis, release, and re-uptake of neurotransmitters in vivo. This non-invasive approach would make it feasible to repeatedly image neural development over time employing these subjects in a variety of behavioral paradigms. This new MRI methods will reveal structural and functional brain alterations during development, making it possible to monitor the neurobiological impact of exposure to drugs.

描述（由申请人提供）：神经生物学和遗传因素无疑会影响药物滥用和成瘾。了解遗传因素如何与大脑发育过程中的环境因素相互作用对于揭示成瘾的病因至关重要。该研究项目的长期目标是开发强大的新工具来研究早期的环境因素（例如围产期压力或暴露于药物）如何有助于在生物学上对成瘾和其他疾病的生物易感性上产生个体差异。最终，该项目旨在使用全氟化神经递质作为成像剂，用于研究具有磁共振成像（MRI）的神经途径的表观遗传。该项目将研究全氟的L-DOPA，并确定用于体内的19F-L-DOPA的最佳异构体。 The project will include developing imaging protocols for detecting the compound at low concentrations, project proposed will include: (1) synthesis, isolation, characterization and purification of perfluoro-tagged isomers of L-DOPA (2) in vitro enzymatic assay characterization of compounds (3) immunoassay screen to characterize the uptake and bioavailability of the novel compounds in vivo, using in ova Gallus域名（4）制定MRI方案，用于使用最佳的全氟烷基标记的异构体。如果有可能直接对与Vivo神经递质的合成，释放和重新摄取有关的特定神经病和事件，将MRI作为研究大脑及其发育的研究工具的实用性将大大增强。 这种非侵入性方法将使随着时间的流逝反复对神经发育进行可行，并在各种行为范式中使用这些受试者。这种新的MRI方法将揭示发育过程中结构和功能性大脑的改变，从而可以监测暴露于药物的神经生物学影响。