Design, Synthesis, and Preliminary Evaluation of SPECT Probes for Imaging β-Amyloid in Alzheimer's Disease Affected Brain
| Autor: | Yoshinari Shoyama, Daisaku Nakamura, Takako Onishi, Yasushi Arano, Akihiro Tanaka, Yoshifumi Maya, Shigeyuki Tanifuji, Hiroki Matsumoto, Yuki Okumura, Izawa Akihiro |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Biodistribution Physiology Cognitive Neuroscience Kinetics Plaque Amyloid Single-photon emission computed tomography Inhibitory postsynaptic potential Biochemistry Iodine Radioisotopes 03 medical and health sciences 0302 clinical medicine Alzheimer Disease medicine Animals Humans Tissue Distribution IC50 Amyloid beta-Peptides medicine.diagnostic_test Chemistry Washout Brain Cell Biology General Medicine In vitro Rats 030104 developmental biology Biophysics Autoradiography 030217 neurology & neurosurgery Emission computed tomography |
| Zdroj: | ACS chemical neuroscience. 9(6) |
| ISSN: | 1948-7193 |
| Popis: | In this study, we synthesized of a series of 2-phenyl- and 2-pyridyl-imidazo[1,2-a]pyridine derivatives and examine their suitability as novel probes for single-photon emission computed tomography (SPECT)-based imaging of β-amyloid (Aβ). Among the 11 evaluated compounds, 10 showed moderate affinity to Aβ(1–42) aggregates, exhibiting half-maximal inhibitory concentrations (IC50) of 14.7 ± 6.07–87.6 ± 39.8 nM. In vitro autoradiography indicated that 123I-labeled triazole-substituted derivatives displayed highly selective binding to Aβ plaques in the hippocampal region of Alzheimer’s disease (AD)-affected brain. Moreover, biodistribution studies performed on normal rats demonstrated that all 123I-labeled probes featured high initial uptake into the brain followed by a rapid washout and were thus well suited for imaging Aβ plaques, with the highest selectivity observed for a 1H-1,2,3-triazole-substituted 2-pyridyl-imidazopyridine derivative, [123I]ABC577. This compound showed good kinetics in rat brain as wel... |
| Databáze: | OpenAIRE |
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