Application of 18F-FDOPA PET in Research of the Association Between HCV Infection and Parkinson's Disease.
Application of 18F-FDOPA PET in Research of the Association Between HCV Infection and Parkinson's Disease.
-[18F]Fluoro-L-3,4-dihydroxyphenylalanine (18F-FDOPA) positron emission tomography (PET) is a
 imaging marker for presynaptic dopaminergic neuronal function. The decreased uptake of
 18F-FDOPA in the posterior putamen is demonstrated in the early course of PD, and could
 differentiate early PD from healthy controls. The objective of this study is to investigate
 the evidence of presynaptic dopaminergic neuronal dysfunction in the preclinical stage of PD,
 which may be associated with HCV infection.
Parkinson's disease (PD) is the second-most neurodegenerative disease in Taiwan. It is
 characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars
 compacta (SNpc). The estimated incidence of PD ranging from 10-18 per 100,000 person-years
 with a tread of increasing number over past decades. Although the exact mechanisms of PD have
 not yet fully clear, many pathological process have shown to be involved in the pathogenesis
 like abnormal alpha-synuclein, activation of microglia and astrocyte, mitochondrial
 dysfunction, oxidative stress, and so on.

 Several characteristics have been considered to increase the risk of having PD. Epidemiologic
 studies have suggested that patients with HCV infection might have higher risk of PD. It is
 common that patients with chronic HCV infection manifest with central nervous system
 manifestations, such as depression, fatigue, and cognitive dysfunction. A previous
 epidemiologic study in Taiwan with a total of 62,276 subjects showed that there is
 significant correlation between PD and hepatitic C virus (HCV) infection. In the study, the
 crude odds ratio for having PD was 1.94 for HCV patients.

 HCV is positive-stranded RNA virus of Flaviviridae family. Flaviviridae family has many
 viruses demonstrating neurotropic character and may be associated with encephalopathy.
 Decreased monoamine transporter binding activity had also been found in HCV infected patients
 who had symptoms of chronic fatigue and cognitive impairment. HCV can cross blood-brain
 barrier and has the ability to replicate in the central nervous system. Animal study has
 shown that HCV infection may up-regulate the inflammatory cytokines, such as sICAM-1, LIX,
 and RANTES, in the rat midbrain neuron-glia coculture and induced dopaminergic neuronal
 toxicity. The elevation of choline/creatine ratio on proton magnetic-resonance spectroscopy
 is also indicative of inflammatory status of brain in patients with chronic HCV infection. it
 is possible that the direct infection of HCV into the brain induce inflammatory status by
 microglia/macrophages and contribute to subsequent neurodegeneration. Chronic HCV infection
 is also associated with systemic cytokine activation including interferon-α and tumor
 necrosis factor α, which may also affect the neuronal function. It has been reported that the
 viral eradication on the patients infected by HCV had change of neurocognitive function.

 6-[18F]Fluoro-L-3,4-dihydroxyphenylalanine (18F-FDOPA) is an analog of
 L-dihydroxyphenylalanine (L-DOPA), which is the precursor of dopamine. L-DOPA is carried into
 the brain through neutral amino acid transport system and converted to domapine by aromatic
 L-amino acid decarboxylase (AADC) in dopaminergic neurons. Use 18F-FDOPA as a tracer of
 positron emission tomography (PET) imaging, the dopamine synthesis rate and presynaptic
 dopaminergic neuronal function can be reflected by the uptake of 18F-FDOPA in dopaminergic
 neurons. The decline of 18F-FDOPA is indicative of dopaminergic neurons dysfunction and can
 be used as imaging marker of the severity of PD. The posterior putamen receives the
 dopaminergic projections from the ventrolateral part of the substantia nigra and is affected
 earliest in the disease course of PD. 18F-FDOPA has been shown its capacity in
 differentiating early PD and healthy controls in previous study with lower metabolism in the
 dorsal putamen even in the early course of PD.

 In this project, 18F-FDOPA PET is used as an imaging marker of striatal dopaminergic
 dysfunction in patients with HCV infection. We will try to detect the subclinical and
 preclinical stages of parkinsonism for these patients.
Adults (older than 20-year-old) with HCV infection and agree to accept 18F-FDOPA PET
 examination.