Fluorodopa is a Promising Fluorine-19 MRI Probe for Evaluating Striatal Dopaminergic Function in a Rat Model of Parkinson's Disease.

Daijiro Yanagisawa,Keisuke Oda,Masatoshi Inden,Takashi Taniguchi,Shigehiro Morikawa,Ikuo Tooyama,Toshiro Inubushi,Masanori Hijioka,Yoshihisa Kitamura

doi:10.1002/jnr.23983

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 potent 19F MRI probe to evaluate dopaminergic presynaptic function in the striatum. To select candidates for 19F 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. In 19F 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 performed 19F MRI in PC12 cells and isolated rat brain using a 7T MR scanner. Our findings suggest that F‐DOPA is a promising 19F MRI probe for evaluating dopaminergic presynaptic function in the striatum of hemiparkinsonian rats. © 2016 Wiley Periodicals, Inc.

Highlights

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra projecting to the striatum
signal-to-noise ratio (S/N) values for haloperidol, GBR13069, GBR12909, 3-bis-FPMT, flupenthixol, and fenfluramine decreased by almost one tenth in brain homogenates, F-DOPA and F-tyrosine displayed relatively higher S/N values in brain homogenates (Fig. 2 and Table I)
We revealed that F-DOPA is a potent 19F magnetic resonance imaging (MRI) probe for evaluating dopaminergic function in the striatum

Summary

Introduction

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra projecting to the striatum. The clinical diagnosis of PD is based on the presence of motor symptoms, including rest tremor, bradykinesia, rigidity, and loss of postural reflexes. It has been estimated that approximately 80% of striatal dopamine (DA) and 50% of nigral dopaminergic neurons are already lost before the onset of typical motor symptom. We revealed that fluorodopa is a potent imaging probe for evaluating dopaminergic function in the striatum in hemiparkinsonian rats. Fluorodopa could be a promising diagnostic agent for Parkinson’s disease, which is characterized by the loss of dopaminergic neurons in the substantia nigra projecting to the striatum.

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