[11C]dihydrotetrabenazine Positron Emission Tomography in Manganese-Exposed Workers

Authors

Susan R. Criswell, Department of Neurology (Dr Criswell, Dr Nielsen, Mr Warden, Dr Perlmutter, Mr Lenox-Krug, Dr Racette); Department of Radiology (Dr Perlmutter, Dr Moerlein); Department of Neuroscience (Dr Perlmutter); Program in Physical Therapy (Dr Perlmutter); Program in Occupational Therapy (Dr Perlmutter); Department of Biochemistry and Molecular Biophysics (Dr Moerlein), Washington University School of Medicine, St. Louis, Missouri ; Department of Environmental and Occupational Health Sciences (Dr Sheppard); Department of Biostatistics (Dr Sheppard), School of Public Health, University of Washington, Seattle, Washington; Department of Family Medicine and Public Health (Dr Checkoway); Department of Neurosciences (Dr Checkoway), School of Medicine, University of California, San Diego, La Jolla, California; Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Parktown, South Africa (Dr Racette).
Susan Searles Nielsen
Mark N. Warden
Joel S. Perlmutter
Stephen M. Moerlein
Lianne Sheppard
Jason Lenox-Krug
Harvey Checkoway
Brad A. Racette

Document Type

Article

Abstract

OBJECTIVE: To understand the neurotoxic effects of manganese (Mn) exposure on monoaminergic function, utilizing [C]dihydrotetrabenazine (DTBZ) positron emission tomography (PET) to measure vesicular monoamine transporter 2 (VMAT2). METHODS: Basal ganglia and thalamic DTBZ binding potentials (BPND) were calculated on 56 PETs from 41 Mn-exposed workers. Associations between cumulative Mn exposure, regional BPND, and parkinsonism were examined by mixed linear regression. RESULTS: Thalamic DTBZ BPND was inversely associated with exposure in workers with less than 3 mg Mn/m-yrs, but subsequently remained stable. Pallidal DTBZ binding increased in workers with less than 2 mg Mn/m-yrs of exposure, but decreased thereafter. Thalamic DTBZ binding was inversely associated with parkinsonism (P = 0.003). CONCLUSION: Mn-dose-dependent associations with thalamic and pallidal DTBZ binding indicate direct effects on monoaminergic VMAT2. Thalamic DTBZ binding was also associated with parkinsonism, suggesting potential as an early biomarker of Mn neurotoxicity.

Medical Subject Headings

Adult; Aged; Carbon Radioisotopes; Female; Humans; Male; Manganese (adverse effects); Middle Aged; Occupational Diseases (chemically induced); Occupational Exposure (adverse effects); Parkinsonian Disorders (chemically induced); Positron-Emission Tomography; Tetrabenazine (analogs & derivatives); Young Adult

Publication Date

10-1-2020

Publication Title

Journal of occupational and environmental medicine

E-ISSN

1536-5948

Volume

62

Issue

10

First Page

788

Last Page

794

PubMed ID

32472844

Digital Object Identifier (DOI)

10.1097/JOM.0000000000001915

Recommended Citation

Criswell, Susan R.; Nielsen, Susan Searles; Warden, Mark N.; Perlmutter, Joel S.; Moerlein, Stephen M.; Sheppard, Lianne; Lenox-Krug, Jason; Checkoway, Harvey; and Racette, Brad A., "[11C]dihydrotetrabenazine Positron Emission Tomography in Manganese-Exposed Workers" (2020). Neurology. 1088.
https://scholar.barrowneuro.org/neurology/1088