[18F]FDOPA positron emission tomography in manganese-exposed workers

• Published in: Neurotoxicology (Park Forest South) Vol. 64; pp. 43 - 49
• Main Authors: Criswell, Susan R., Nielsen, Susan Searles, Warden, Mark, Perlmutter, Joel S., Moerlein, Stephen M., Flores, Hubert P., Huang, John, Sheppard, Lianne, Seixas, Noah, Checkoway, Harvey, Racette, Brad A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2018; Elsevier BV
• Subjects: [18F]FDOPA PET; Brain; Brain diseases; Confidence intervals; Dihydroxyphenylalanine; Dopamine receptors; Emission analysis; Exposure; Human exposure; Levodopa; Magnetic resonance imaging; Manganese; Metal workers; Movement disorders; Neostriatum; Neurodegenerative diseases; Neuroimaging; Neurotoxicity; NMR; Nuclear magnetic resonance; Occupational exposure; Parkinson's disease; Positron emission; Positron emission tomography; Putamen; Regression analysis; Statistical analysis; Tomography; Welding; Welding machines; [18F]FDOPA PET; Manganese; [F]FDOPA PET
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2017.07.004

•The underlying mechanism of manganese neurotoxicity remains unknown.•FDOPA PET is a non-invasive method assessing dopaminergic neuronal function.•Mn-exposed welders and workers demonstrated lower caudate FDOPA uptake.•Mn-exposure is associated with pre-synaptic dopaminergic dysfunction. Occupational manganese (Mn) exposure is associated with the development of parkinsonism; however, the mechanism of neurotoxicity is unknown. Brain positron emission tomography (PET) imaging provides a non-invasive method of assessing dopamineric neuronal function. 6-[18F]fluoro-L-DOPA (FDOPA) PET reflects in-vivo nigrostriatal function, but results in Mn exposure are conflicting. The objective of this study was to investigate the association between Mn exposure secondary to occupational welding, FDOPA striatal uptake, and clinical parkinsonism as measured by Unified Parkinson Disease Rating Scale motor subscore 3 (UPDRS3) scores. FDOPA PET scans were acquired on 72 subjects (27 Mn-exposed welders, 14 other Mn-exposed workers, and 31 non-exposed subjects). We estimated cumulative welding exposure from detailed work histories, and a movement disorders specialist examined all subjects. Striatal volumes of interest were identified on aligned magnetic resonance imaging (MRI) for each subject. Specific striatal FDOPA uptake was calculated with a graphical analysis method. We used linear regression while adjusting for age to assess the association between welding exposure and FDOPA uptake in the caudate, anterior putamen, and posterior putamen. Compared to the non-exposed subjects, mean caudate FDOPA uptake was 0.0014min−1 (95% confidence interval [CI] 0.0008, 0.0020) lower in Mn-exposed welders and 0.0012min−1 (95% CI 0.0005, 0.0019) lower in other Mn-exposed workers (both p≤0.001). There was no clear dose-response association between caudate FDOPA uptake and Mn exposure or UPDRS3 scores. Mn-exposed welders and workers demonstrated lower caudate FDOPA uptake, indicating pre-synaptic dopaminergic dysfunction in Mn-exposed subjects that was not associated with clinical parkinsonism.