title: Quantitative analysis of the therapeutic effect of magnolol on MPTP-induced mouse model of Parkinson's disease using in vivo 18F-9-fluoropropyl-(+)-dihydrotetrabenazine PET imaging.
abstract: 18F-9-Fluoropropyl-(+)-dihydrotetrabenazine [18F-FP-(+)-DTBZ] positron emission tomography (PET) has been shown to detect dopaminergic neuron loss associated with Parkinson's disease (PD) in human and neurotoxin-induced animal models. A polyphenol compound, magnolol, was recently proposed as having a potentially restorative effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 6-hydroxydopamine-treated animal models. In this study, 18F-FP-(+)-DTBZ PET was used to determine the therapeutic efficacy of magnolol in an MPTP-PD mouse model that was prepared by giving an intraperitoneally (i.p.) daily dose of 25 mg/kg MPTP to male C57BL/6 mice for 5 consecutive days. Twenty-minute static 18F-FP-(+)-DTBZ PET scans were performed before MPTP treatment and 5 days after the termination of MPTP treatment to set up the baseline control. Half of the MPTP-treated mice then received a daily dose of magnolol (10 mg/kg dissolved in corn oil, i.p.) for 6 days. 18F-FP-(+)-DTBZ PET imaging was performed the day after the final treatment. All 18F-FP-(+)-DTBZ PET images were analysed and the specific uptake ratio (SUr) was calculated. Ex vivo autoradiography (ARG) and corresponding immunohistochemistry (IHC) studies were conducted to confirm the distribution of dopaminergic terminals in the striatum. The striatal SUr ratios of 18F-FP-(+)-DTBZ PET images for the Sham, the MPTP, and the MPTP + Magnolol-treated groups were 1.25 ± 0.05, 0.75 ± 0.06, and 1.00 ± 0.11, respectively (n = 4 for each group). The ex vivo 18F-FP-(+)-DTBZ ARG and IHC results correlated favourably with the PET imaging results. 18F-FP-(+)-DTBZ PET imaging suggested that magnolol post-treatment may reverse the neuronal damage in the MPTP-lesioned PD mice. In vivo imaging of the striatal vesicular monoamine transporter type 2 (VMAT2) distribution using 18F-FP-(+)-DTBZ animal PET is a useful method to evaluate the efficacy of therapeutic drugs i.e., magnolol, for the management of PD.
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan.|Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chi-Chang
authors.initials: CC
authors.lastname: Weng
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Zi-An
authors.initials: ZA
authors.lastname: Chen
authors.affiliation: Center for Advanced Molecular Imaging and Translation, Department of Nuclear Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
authors.forename: Ko-Ting
authors.initials: KT
authors.lastname: Chao
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Ting-Wei
authors.initials: TW
authors.lastname: Ee
authors.affiliation: Center for Advanced Molecular Imaging and Translation, Department of Nuclear Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.|Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
authors.forename: Kun-Ju
authors.initials: KJ
authors.lastname: Lin
authors.affiliation: Institute of Neuroscience, National Chengchi University, Taipei, Taiwan.
authors.forename: Ming-Huan
authors.initials: MH
authors.lastname: Chan
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan.|Center for Advanced Molecular Imaging and Translation, Department of Nuclear Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.|Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
authors.forename: Ing-Tsung
authors.initials: IT
authors.lastname: Hsiao
authors.affiliation: Center for Advanced Molecular Imaging and Translation, Department of Nuclear Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Mei-Ping
authors.initials: MP
authors.lastname: Kung
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Ching-Han
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan.|Center for Advanced Molecular Imaging and Translation, Department of Nuclear Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.|Institute of Radiological Research, Chang Gung University and Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Shiaw-Pyng
authors.identifier: http://orcid.org/0000-0002-7222-2601
authors.initials: SP
authors.lastname: Wey
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes / Q000008:administration & dosage; D006801:Humans; D017705:Lignans / Q000008:administration & dosage*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000188:drug therapy*; D049268:Positron-Emission Tomography; D013747:Tetrabenazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
chemical_list: D001713:Biphenyl Compounds; D005462:Fluorine Radioisotopes; D017705:Lignans; C493453:Slc18a2 protein, mouse; D050493:Vesicular Monoamine Transport Proteins; C005498:magnolol; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C549477:florbenazine F 18; D013747:Tetrabenazine