A Novel Near-Infrared Fluorescence Probe THK-565 Enables In Vivo Detection of Amyloid Deposits in Alzheimer’s Disease Mouse Model

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>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 <jats:italic>in vivo</jats:italic> detection of protein deposits without radiation exposure. Comprehensive screening of fluorescent compounds identified a novel compound, THK-565, for the <jats:italic>in vivo</jats:italic> imaging of amyloid-β (Aβ) deposits in the mouse brain. This study assessed whether THK-565 could detect amyloid-β deposits <jats:italic>in vivo</jats:italic> in the AD mouse model.</jats:p> </jats:sec><jats:sec> <jats:title>Procedures</jats:title> <jats:p>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. <jats:italic>In vivo</jats:italic> 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.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>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. <jats:italic>Ex vivo</jats:italic> analysis confirmed that the THK-565 signal corresponded to Aβ immunostaining in the brain sections of these mice.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>A novel NIRF probe, THK-565, enabled the <jats:italic>in vivo</jats:italic> 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.</jats:p> </jats:sec>