TY - JOUR
T1 - [11C]dihydrotetrabenazine Positron Emission Tomography in Manganese-Exposed Workers
AU - Criswell, Susan R.
AU - Nielsen, Susan Searles
AU - Warden, Mark N.
AU - Perlmutter, Joel S.
AU - Moerlein, Stephen M.
AU - Sheppard, Lianne
AU - Lenox-Krug, Jason
AU - Checkoway, Harvey
AU - Racette, Brad A.
N1 - Publisher Copyright:
© 2020 Lippincott Williams and Wilkins. All rights reserved.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Objective:To understand the neurotoxic effects of manganese (Mn) exposure on monoaminergic function, utilizing [11C]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/m3-yrs, but subsequently remained stable. Pallidal DTBZ binding increased in workers with less than 2 mg Mn/m3-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.
AB - Objective:To understand the neurotoxic effects of manganese (Mn) exposure on monoaminergic function, utilizing [11C]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/m3-yrs, but subsequently remained stable. Pallidal DTBZ binding increased in workers with less than 2 mg Mn/m3-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.
KW - manganese
KW - parkinsonism
KW - positron emission tomography
KW - vesicular monoamine transporter 2
UR - http://www.scopus.com/inward/record.url?scp=85092680111&partnerID=8YFLogxK
U2 - 10.1097/JOM.0000000000001915
DO - 10.1097/JOM.0000000000001915
M3 - Article
C2 - 32472844
AN - SCOPUS:85092680111
SN - 1076-2752
VL - 62
SP - 788
EP - 794
JO - Journal of occupational and environmental medicine
JF - Journal of occupational and environmental medicine
IS - 10
ER -