論文 - 詳細
| RRC ID | 88538 |
|---|---|
| 著者 | Naganuma F, Murata D, Inoue M, Maehori Y, Harada R, Furumoto S, Kudo Y, Nakamura T, Okamura N. |
| タイトル | A Novel Near-Infrared Fluorescence Probe THK-565 Enables In Vivo Detection of Amyloid Deposits in Alzheimer's Disease Mouse Model. |
| ジャーナル | Mol Imaging Biol |
| Abstract |
PURPOSE:Noninvasive imaging of protein aggregates in the brain is critical for the early diagnosis, disease monitoring, and evaluation of the effectiveness of novel therapies for Alzheimer's disease (AD). Near-infrared fluorescence (NIRF) imaging with specific probes is a promising technique for the in vivo detection of protein deposits without radiation exposure. Comprehensive screening of fluorescent compounds identified a novel compound, THK-565, for the in vivo imaging of amyloid-β (Aβ) deposits in the mouse brain. This study assessed whether THK-565 could detect amyloid-β deposits in vivo in the AD mouse model. PROCEDURES:The fluorescent properties of THK-565 were evaluated in the presence and absence of Aβ fibrils. APP knock-in (APP-KI) mice were used as an animal model of AD. In vivo NIRF images were acquired after the intravenous administration of THK-565 and THK-265 in mice. The binding selectivity of THK-565 to Aβ was evaluated using brain slices obtained from these mouse models. RESULTS:The fluorescence intensity of the THK-565 solution substantially increased by mixing with Aβ fibrils. The maximum emission wavelength of the complex of THK-565 and Aβ fibrils was 704 nm, which was within the optical window range. THK-565 selectively bound to amyloid deposits in brain sections of APP-KI mice After the intravenous administration of THK-565, the fluorescence signal in the head of APP-KI mice was significantly higher than that of wild-type mice and higher than that after administration of THK-265. Ex vivo analysis confirmed that the THK-565 signal corresponded to Aβ immunostaining in the brain sections of these mice. CONCLUSIONS:A novel NIRF probe, THK-565, enabled the in vivo detection of Aβ deposits in the brains of the AD mouse model, suggesting that NIRF imaging with THK-565 could non-invasively assess disease-specific pathology in AD. |
| 巻・号 | 25(6) |
| ページ | 1115-1124 |
| 公開日 | 2023-12-1 |
| DOI | 10.1007/s11307-023-01843-4 |
| PII | 10.1007/s11307-023-01843-4 |
| PMID | 37580462 |
| PMC | PMC10728248 |
| MeSH | Alzheimer Disease* / metabolism Amyloid / metabolism Amyloid beta-Peptides / metabolism Animals Brain / metabolism Disease Models, Animal Fluorescent Dyes / chemistry Mice Mice, Transgenic Plaque, Amyloid / metabolism Pyrimidinones Thiones |
| リソース情報 | |
| 実験動物マウス | RBRC06344 |