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

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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.