| First Author | Naganuma F | Year | 2023 |
| Journal | Mol Imaging Biol | Volume | 25 |
| Issue | 6 | Pages | 1115-1124 |
| PubMed ID | 37580462 | Mgi Jnum | J:347261 |
| Mgi Id | MGI:7616646 | Doi | 10.1007/s11307-023-01843-4 |
| Citation | Naganuma F, et al. (2023) A Novel Near-Infrared Fluorescence Probe THK-565 Enables In Vivo Detection of Amyloid Deposits in Alzheimer's Disease Mouse Model. Mol Imaging Biol 25(6):1115-1124 |
| abstractText | 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-beta (Abeta) deposits in the mouse brain. This study assessed whether THK-565 could detect amyloid-beta deposits in vivo in the AD mouse model. PROCEDURES: The fluorescent properties of THK-565 were evaluated in the presence and absence of Abeta 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 Abeta was evaluated using brain slices obtained from these mouse models. RESULTS: The fluorescence intensity of the THK-565 solution substantially increased by mixing with Abeta fibrils. The maximum emission wavelength of the complex of THK-565 and Abeta 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 Abeta immunostaining in the brain sections of these mice. CONCLUSIONS: A novel NIRF probe, THK-565, enabled the in vivo detection of Abeta 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. |
