title: Fluorodopa is a Promising Fluorine-19 MRI Probe for Evaluating Striatal Dopaminergic Function in a Rat Model of Parkinson's Disease.
abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra projecting to the striatum. It has been estimated that approximately 80% of the striatal dopamine and 50% of nigral dopaminergic neurons are lost before the onset of typical motor symptoms, indicating that early diagnosis of PD using noninvasive imaging is feasible. Fluorine-19 (19F) magnetic resonance imaging (MRI) represents a highly sensitive, easily available, low-background, and cost-effective approach to evaluate dopaminergic function using non-radioactive fluorine-containing dopaminergic agents. The aim of this study was to find a potent19F MRI probe to evaluate dopaminergic presynaptic function in the striatum. To select candidates for19F MRI probes, we investigated the following eight non-radioactive fluorine-containing dopaminergic agents: fluorodopa (F-DOPA), F-tyrosine, haloperidol, GBR13069 duhydrochloride, GBR12909 duhydrochloride, 3-bis-(4-fluorophenyl) methoxytropane hydrochloride, flupenthixol, and fenfluramine. In19F nuclear magnetic resonance measurements, F-tyrosine and F-DOPA displayed a relatively higher signal-to-noise ratio value in brain homogenates than in others. F-DOPA, but not F-tyrosine, induced the rotational behavior in a 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian rat model. In addition, a significantly high amount of F-DOPA accumulated in the ipsilateral striatum of hemiparkinsonian rats after the injection. We performed19F MRI in PC12 cells and isolated rat brain using a 7T MR scanner. Our findings suggest that F-DOPA is a promising19F MRI probe for evaluating dopaminergic presynaptic function in the striatum of hemiparkinsonian rats. © 2016 Wiley Periodicals, Inc.
authors: Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, 520-2192, Japan.
authors: Daijiro
authors: D
authors: Yanagisawa
authors: Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, 520-2192, Japan.|Department of Neurobiology, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Yamashina-ku, Kyoto, 607-8414, Japan.
authors: Keisuke
authors: K
authors: Oda
authors: Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, 1-25-4, Daigaku-Nishi, Gifu, 501-1196, Japan.
authors: Masatoshi
authors: M
authors: Inden
authors: Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, 520-2192, Japan.
authors: Shigehiro
authors: S
authors: Morikawa
authors: Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, 520-2192, Japan.
authors: Toshiro
authors: T
authors: Inubushi
authors: Department of Neurobiology, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Yamashina-ku, Kyoto, 607-8414, Japan.
authors: Takashi
authors: T
authors: Taniguchi
authors: Laboratory of Pharmacology and Neurobiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1, Noji-higashi, Kusatsu, 525-8577, Japan.
authors: Masanori
authors: M
authors: Hijioka
authors: Laboratory of Pharmacology and Neurobiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1, Noji-higashi, Kusatsu, 525-8577, Japan.
authors: Yoshihisa
authors: Y
authors: Kitamura
authors: Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, 520-2192, Japan.
authors: Ikuo
authors: I
authors: Tooyama
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000502:physiology; D005461:Fluorine / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000378:metabolism; D066235:Fluorine-19 Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D016716:PC12 Cells; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005462:Fluorine Radioisotopes; D005461:Fluorine; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004298:Dopamine
keywords: Parkinson's disease; dopaminergic neuron; fluorine-19 MRI; fluorodopa