Development of a novel radioiodinated compound for amyloid and tau deposition imaging in Alzheimer's disease and tauopathy mouse models
Year: 2024
Type: article
Abstract: Non-invasive determination of amyloid-β peptide (Aβ) and tau deposition are important for early diagnosis and therapeutic intervention for Alzheimer's disease (AD) and non-AD tauopathies. In the present study, we investigated the capacity of a novel radioiodinated compound AD-DRK (123/125I-AD-DRK) with 50% inhibitory concentrations of 11 nM and 2 nM for Aβ and tau aggregates, respectively, as a single photon emission computed tomography (SPECT) ligand in living brains. In vitro and ex vivo autoradiography with 125I-AD-DRK was performed in postmortem human and two transgenic (Tg) mice lines with either fibrillar Aβ or tau accumulation, APP23 and rTg4510 mice. SPECT imaging of 123I-AD-DRK was performed in APP23 mice to investigate the ability of AD-DRK to visualize fibrillar protein deposition in the living brain. In-vitro autoradiogram of 125I-AD-DRK showed high specific radioactivity accumulation in the temporal cortex and hippocampus of AD patients and the motor cortex of progressive supranuclear palsy (PSP) patients enriched by Aβ and/or tau aggregates. Ex-vivo autoradiographic images also demonstrated a significant increase in 125I-AD-DRK binding in the forebrain of both APP23 and rTg450 mice compared to their corresponding non-Tg littermates. SPECT imaging successfully captured Aβ deposition in the living brain of aged APP23 mice. The present study developed a novel high-contrast SPECT agent for assisting the diagnosis of AD and non-AD tauopathies, likely benefiting from its affinity for both fibrillar Aβ and tau.
Authors: Rui, Xiyan, Zhao, Xinran, Zhang, Nailian, Ding, Yuzhou, Seki, Chie, Ono, Maiko, Higuchi, Makoto, Zhang, Ming-Rong, Chu, Yong, Wei, Ruonan, Xu, Miaomiao, Cheng, Chao, Zuo, Changjing, Kimura, Yasuyuki, Ni, Ruiqing, Kai, Mototora, Tian, Mei, Yuan, Chunyan, Ji, Bin
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6966692411
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