title: Preliminary Characterization and In Vivo Studies of Structurally Identical (18)F- and (125)I-Labeled Benzyloxybenzenes for PET/SPECT Imaging of β-Amyloid Plaques.
abstract: With the assistance of molecular docking and 3D-QSAR models established previously, structurally identical (18)F- and (125)I-labeled benzyloxybenzene derivatives were designed to achieve the early detection of Aβ plaques by PET/SPECT imaging. In competition binding assay, ligands 7a and 12a displayed high binding affinities to Aβ42 aggregates with Ki values of 19.5 nM and 23.9 nM, respectively. Specific plaque labeling was observed on the in vitro autoradiography of brain sections from AD patients and Tg mice. In biodistribution, [(125)I]7a, [(18)F]7a, [(125)I]12a and [(18)F]12a all exhibited high initial brain uptakes (>5% ID/g at 2 min). [(125)I]7a and [(125)I]12a cleared fast from the normal brain regions, while corresponding [(18)F]7a and [(18)F]12a showed slow washout rates. Dynamic microPET/CT and microSPECT/CT imaging data in normal ICR mice were in accordance with in vivo biodistribution results. In vivo metabolism results indicated that the different clearance profiles between the structurally identical (18)F- and (125)I-labeled tracers could be attributed to different biochemical characteristics of the radiometabolites. Radioiodinated benzyloxybenzene derivatives exhibited good in vivo biostability in brain. Ex vivo autoradiography further confirmed the strong in vivo Aβ labeling ability of [(125)I]7a. These new fluorinated and iodinated benzyloxybenzenes can develop into PET/SPECT dual imaging agents targeting Aβ plaques.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Cui
authors.affiliation: Department of Nuclear Medicine, Chinese PLA General Hospital, Beijing 100853, P. R. China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China.
authors.forename: Zhide
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China.
authors.forename: Yesen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan 430074, P. R. China.
authors.forename: Jiapei
authors.initials: J
authors.lastname: Dai
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.
authors.forename: Boli
authors.initials: B
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005462:Fluorine Radioisotopes; D057927:Hydrophobic and Hydrophilic Interactions; D007457:Iodine Radioisotopes; D051379:Mice; D008958:Models, Molecular; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology*; D049268:Positron-Emission Tomography / Q000379:methods; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological; D011487:Protein Conformation; D019275:Radiopharmaceuticals; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014057:Tomography, X-Ray Computed
chemical_list: D016229:Amyloid beta-Peptides; D005462:Fluorine Radioisotopes; D007457:Iodine Radioisotopes; D066329:Protein Aggregates; D019275:Radiopharmaceuticals