Chronic manganism: A long-term follow-up study with a new dopamine terminal biomarker of 18F-FP-(+)-DTBZ (18F-AV-133) brain PET scan.
Recent experimental studies revealed that dopamine neuron dysfunction in chronic manganism may be due to a reduced capacity of dopamine release in the striatum. The findings imposed further difficulty in the differential diagnosis between manganism and IPD. We conducted a long-term clinical follow-up study of 4 manganism patients, applying a new tracer (18)F-9-fluoropropyl-(+)-dihydrotetrabenazine ((18)F-AV-133) with positron emission tomography (PET). Twenty age-matched subjects including 4 manganism patients, 8 idiopathic Parkinson's disease (IPD) patients, and 8 healthy controls were enrolled for comparison. Volumes of interest of the bilateral putamen, caudate nuclei and occipital cortex as the reference region were delineated from individual magnetic resonance images. The clinical features of the manganism patients still progressed, with increased scores on the Unified Parkinson Disease Rating Scale. The (18)F-AV-133 uptake in the IPD patients decreased at the bilateral striatum, compared with the healthy controls. In the manganism patients, there was no decreased uptake of radioactivity involving the bilateral striatum, except Patient 4, who had a stroke with decreased uptake in the right posterior putamen. The (18)F-AV-133 PET finding reveals that nigrostriatum neurons are not degenerated in chronic manganism and can provide a useful neuroimage biomarker in the differential diagnosis.
Department of Neurology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Chu-Yun
CY
Huang
Department of Neurology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, Division of Medical Education, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Chi-Hung
CH
Liu
Department of Family Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Environmental and Occupational Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Eusden
E
Tsao
Molecular Imaging Center and Nuclear Medicine, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Healthy Aging Research Center Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Chia-Ju
CJ
Hsieh
Department of Neurology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Neurology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Yi-Hsin
YH
Weng
Molecular Imaging Center and Nuclear Medicine, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Healthy Aging Research Center Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Ing-Tsung
IT
Hsiao
Molecular Imaging Center and Nuclear Medicine, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Healthy Aging Research Center Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Tzu-Chen
TC
Yen
Molecular Imaging Center and Nuclear Medicine, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Healthy Aging Research Center Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Kun-Ju
KJ
Lin
Department of Neurology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Neurology, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: cch0537@adm.cgmh.org.tw.
Chin-Chang
CC
Huang
D018759:Adrenergic Uptake Inhibitors / Q000493:pharmacokinetics*; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D016022:Case-Control Studies; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020149:Manganese Poisoning / Q000000981:diagnostic imaging*; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D049268:Positron-Emission Tomography; D013624:Taiwan; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015898:Tomography Scanners, X-Ray Computed
D018759:Adrenergic Uptake Inhibitors; D005462:Fluorine Radioisotopes; C549477:florbenazine F 18; D004298:Dopamine; D013747:Tetrabenazine
(18)F-AV-133; (18)F-FP-(+)-DTBZ; IPD; Manganese; Positron emission tomography; Type 2 vesicle monoamine transporter