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

PF-L-DOPA：发育神经生物学的 MRI 工具

基本信息

批准号：
7116038
负责人：
SHERRY DINGMAN
金额：
$ 3.25万
依托单位：
MARIST COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-30 至 2006-06-30
项目状态：
已结题

项目摘要

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肯定会影响药物滥用和成瘾。了解大脑发育过程中遗传因素如何与环境因素相互作用，对于解开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，用于调查早期环境因素，如围产期压力或暴露于药物，如何有助于在成瘾和其他疾病的生物易感性方面产生个体差异。最终，该项目旨在使用全氟神经递质作为成像剂，通过磁共振成像（MRI）研究神经通路的表观发生。本项目将研究全氟左旋多巴，并确定用于体内的19 F-L-多巴的最佳异构体。该项目将包括开发成像协议，用于检测低浓度的化合物，拟议项目将包括：（1）全氟标记的L-DOPA异构体的合成、分离、表征和纯化（2）化合物的体外酶测定表征（3）免疫测定筛选以表征新化合物的体内摄取和生物利用度，（4）设计使用最佳全氟烷基标记异构体的MRI方案。MRI作为研究大脑及其发育的研究工具的有用性将大大增强，如果它能够直接成像特定的神经通路和与体内神经递质的合成，释放和再摄取相关的事件。这种非侵入性的方法将使其可行的重复图像神经发育随着时间的推移，采用这些科目在各种行为范例。这种新的MRI方法将揭示发育过程中大脑结构和功能的变化，从而有可能监测暴露于药物的神经生物学影响。