Synthesis and evaluation of novel ¹⁸F labeled 2-pyridinylbenzoxazole and 2-pyridinylbenzothiazole derivatives as ligands for positron emission tomography (PET) imaging of β-amyloid plaques
| Autor: | Mengchao, Cui, Xuedan, Wang, Pingrong, Yu, Jinming, Zhang, Zijing, Li, Xiaojun, Zhang, Yanping, Yang, Masahiro, Ono, Hongmei, Jia, Hideo, Saji, Boli, Liu |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Benzoxazoles Fluorine Radioisotopes Amyloid beta-Peptides Pyridines Brain Mice Transgenic Plaque Amyloid Ligands Binding Competitive Peptide Fragments Polyethylene Glycols Mice Radioligand Assay Structure-Activity Relationship Drug Stability Positron-Emission Tomography Animals Autoradiography Humans Tissue Distribution Benzothiazoles Radiopharmaceuticals |
| Zdroj: | Journal of medicinal chemistry. 55(21) |
| ISSN: | 1520-4804 |
| Popis: | A series of fluoro-pegylated (FPEG) 2-pyridinylbenzoxazole and 2-pyridinylbenzothiazole derivatives were synthesized and evaluated as novel β-amyloid (Aβ) imaging probes for PET. They displayed binding affinities for Aβ(1-42) aggregates that varied from 2.7 to 101.6 nM. Seven ligands with high affinity were selected for (18)F labeling. In vitro autoradiography results confirmed the high affinity of these radiotracers. In vivo biodistribution experiments in normal mice indicated that the radiotracers with a short FPEG chain (n = 1) displayed high initial uptake into and rapid washout from the brain. One of the 2-pyridinylbenzoxazole derivatives, [(18)F]-5-(5-(2-fluoroethoxy)benzo[d]oxazol-2-yl)-N-methylpyridin-2-amine ([(18)F]32) (K(i) = 8.0 ± 3.2 nM) displayed a brain(2min)/brain(60min) ratio of 4.66, which is highly desirable for Aβ imaging agents. Target specific binding of [(18)F]32 to Aβ plaques was validated by ex vivo autoradiographic experiment with transgenic model mouse. Overall, [(18)F]32 is a promising Aβ imaging agent for PET and merits further evaluation in human subjects. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|