florbenazine-f-18 and Parkinson-Disease--Secondary

Although parkinsonism after carbon monoxide (CO) intoxication is well known, neurotransmitter deficient networks that are responsible for the severity of parkinsonism have rarely been systemically evaluated.. Eighteen patients with CO-related parkinsonism and nine age- and sex-matched controls were enrolled for detailed neurological examinations, three-dimensional T1-weighted images, diffusion tensor imaging and (18)F-9-fluoropropyl-(+)-dihydrotetrabenzazine ((18)F-FP-(+)-DTBZ) positron emission tomography (PET). The structural analysis included voxel-based morphometry to assess grey matter atrophy and tract-based spatial statistics related to white matter involvement. For presynaptic monoaminergic assessment, volume of interest analysis in six subcortical regions and non-parametric voxel-wise comparison were performed on PET images with estimation of registration parameters from magnetic resonance images. All the imaging modalities were compared between the patients and controls. For the patients, a regression model for correlation with cognitive behaviour and Unified Parkinson's Disease Rating Scale (UPDRS) score was used.. In the patients, monoaminergic deficit networks were found in the caudate, anterior putamen, anterior insular, thalamus and anterior cingulate cortex. The UPDRS revealed significant correlations with the prefrontal white matter fractional anisotropy values and with the (18)F-FP-(+)-DTBZ uptake values in the caudate nucleus, insular, medial prefrontal and dorsomedial thalamus. The neuropsychiatric inventory score correlated with the (18)F-FP-(+)-DTBZ uptake values in the anterior cingulate cortex and dorsolateral prefrontal cortex.. Our study demonstrated monoaminergic deficits and white matter damage networks in CO-related parkinsonism that determined the severity of parkinsonism or behaviour changes. As the substantia nigra was spared, the monoaminergic topography of involvement suggests a different pathophysiology in CO-related parkinsonism.

Topics: Adult; Biogenic Monoamines; Carbon Monoxide Poisoning; Female; Fluorine Radioisotopes; Humans; Male; Middle Aged; Parkinson Disease, Secondary; Positron-Emission Tomography; Severity of Illness Index; Tetrabenazine; White Matter

18F-9-Fluoropropyl-(+)-dihydrotetrabenazine [18F-FP-(+)-DTBZ] positron emission tomography (PET) has been shown to detect dopaminergic neuron loss associated with Parkinson's disease (PD) in human and neurotoxin-induced animal models. A polyphenol compound, magnolol, was recently proposed as having a potentially restorative effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 6-hydroxydopamine-treated animal models. In this study, 18F-FP-(+)-DTBZ PET was used to determine the therapeutic efficacy of magnolol in an MPTP-PD mouse model that was prepared by giving an intraperitoneally (i.p.) daily dose of 25 mg/kg MPTP to male C57BL/6 mice for 5 consecutive days. Twenty-minute static 18F-FP-(+)-DTBZ PET scans were performed before MPTP treatment and 5 days after the termination of MPTP treatment to set up the baseline control. Half of the MPTP-treated mice then received a daily dose of magnolol (10 mg/kg dissolved in corn oil, i.p.) for 6 days. 18F-FP-(+)-DTBZ PET imaging was performed the day after the final treatment. All 18F-FP-(+)-DTBZ PET images were analysed and the specific uptake ratio (SUr) was calculated. Ex vivo autoradiography (ARG) and corresponding immunohistochemistry (IHC) studies were conducted to confirm the distribution of dopaminergic terminals in the striatum. The striatal SUr ratios of 18F-FP-(+)-DTBZ PET images for the Sham, the MPTP, and the MPTP + Magnolol-treated groups were 1.25 ± 0.05, 0.75 ± 0.06, and 1.00 ± 0.11, respectively (n = 4 for each group). The ex vivo 18F-FP-(+)-DTBZ ARG and IHC results correlated favourably with the PET imaging results. 18F-FP-(+)-DTBZ PET imaging suggested that magnolol post-treatment may reverse the neuronal damage in the MPTP-lesioned PD mice. In vivo imaging of the striatal vesicular monoamine transporter type 2 (VMAT2) distribution using 18F-FP-(+)-DTBZ animal PET is a useful method to evaluate the efficacy of therapeutic drugs i.e., magnolol, for the management of PD.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Biphenyl Compounds; Corpus Striatum; Disease Models, Animal; Fluorine Radioisotopes; Humans; Lignans; Mice; Neurons; Parkinson Disease; Parkinson Disease, Secondary; Positron-Emission Tomography; Tetrabenazine; Vesicular Monoamine Transport Proteins