Preliminary Characterization and In Vivo Studies of Structurally Identical 18F- and 125I-Labeled Benzyloxybenzenes for PET/SPECT Imaging of β-Amyloid Plaques
| Autor: | Xiaoyang Zhang, Mengchao Cui, Yesen Li, Xianzhong Zhang, Jinming Zhang, Yanping Yang, Zhide Guo, Jiapei Dai, Boli Liu |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Biodistribution Pathology medicine.medical_specialty Fluorine Radioisotopes Protein Conformation Plaque Amyloid Protein Aggregation Pathological Article Iodine Radioisotopes Mice Protein Aggregates In vivo Alzheimer Disease Spect imaging medicine Animals Tomography Emission-Computed Single-Photon Multidisciplinary Amyloid beta-Peptides medicine.diagnostic_test Chemistry Ligand binding assay Brain medicine.disease Molecular biology In vitro Positron emission tomography Positron-Emission Tomography Alzheimer's disease Radiopharmaceuticals Tomography X-Ray Computed Hydrophobic and Hydrophilic Interactions Ex vivo |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep12084 |
| Popis: | With the assistance of molecular docking and 3D-QSAR models established previously, structurally identical 18F- and 125I-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, [125I]7a, [18F]7a, [125I]12a and [18F]12a all exhibited high initial brain uptakes (>5% ID/g at 2 min). [125I]7a and [125I]12a cleared fast from the normal brain regions, while corresponding [18F]7a and [18F]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 18F- and 125I-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 [125I]7a. These new fluorinated and iodinated benzyloxybenzenes can develop into PET/SPECT dual imaging agents targeting Aβ plaques. |
| Databáze: | OpenAIRE |
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