[11C]二氢四苯并嗪正电子发射断层扫描在锰暴露工人中的应用。
[11C]dihydrotetrabenazine Positron Emission Tomography in Manganese-Exposed Workers.
机构信息
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).
出版信息
J Occup Environ Med. 2020 Oct;62(10):788-794. doi: 10.1097/JOM.0000000000001915.
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.
目的
利用[C]二氢去甲替林（DTBZ）正电子发射断层扫描（PET）测量囊泡单胺转运体 2（VMAT2），了解锰（Mn）暴露对单胺能功能的神经毒性作用。
方法
对 41 名 Mn 暴露工人的 56 次 PET 计算基底节和丘脑 DTBZ 结合势（BPND）。采用混合线性回归分析累积 Mn 暴露、区域 BPND 与帕金森病之间的关系。
结果
暴露于 Mn 量小于 3mg/m-yrs 的工人，丘脑 DTBZ BPND 与暴露呈负相关，但随后保持稳定。暴露于 Mn 量小于 2mg/m-yrs 的工人的苍白球 DTBZ 结合增加，但随后减少。丘脑 DTBZ 结合与帕金森病呈负相关（P=0.003）。
结论
与丘脑和苍白球 DTBZ 结合的 Mn 剂量依赖性关联表明其对单胺能 VMAT2 有直接作用。丘脑 DTBZ 结合也与帕金森病相关，提示其可能作为 Mn 神经毒性的早期生物标志物。
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