Related Experiment Video
Updated: Dec 20, 2025
Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
[11C]dihydrotetrabenazine Positron Emission Tomography in Manganese-Exposed Workers
Susan R Criswell1, Susan Searles Nielsen, Mark N Warden
1Department 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).
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.
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