Department of Radiopharmacy and Molecular Imaging, Minhang Hospital & School of Pharmacy, Fudan University, Shanghai, China; Institute for Small-Molecule Drug Discovery & Development, Quzhou Fudan Institute, Quzhou, China.
Department of Functional Brain Imaging Research, China.
Neuroimage. 2024 Dec 1;303:120947. doi: 10.1016/j.neuroimage.2024.120947. Epub 2024 Nov 19.
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 (I-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 I-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 I-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 I-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 I-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.
非侵入性测定淀粉样β肽（Aβ）和 tau 沉积对于阿尔茨海默病（AD）和非 AD tau 病的早期诊断和治疗干预非常重要。在本研究中，我们研究了一种新型放射性碘标记化合物 AD-DRK（I-AD-DRK）的能力，其对 Aβ和 tau 聚集的 50%抑制浓度分别为 11 nM 和 2 nM，作为单光子发射计算机断层扫描（SPECT）配体在活脑中。使用 I-AD-DRK 进行了死后人和两种转基因（Tg）小鼠（分别具有纤维状 Aβ或 tau 积累的 APP23 和 rTg4510 小鼠）的体外和离体放射自显影。在 APP23 小鼠中进行了 I-AD-DRK 的 SPECT 成像，以研究 AD-DRK 可视化活脑中纤维状蛋白沉积的能力。I-AD-DRK 的体外放射自显影显示，在 AD 患者的颞叶皮层和海马以及富含 Aβ和/或 tau 聚集物的进行性核上麻痹（PSP）患者的运动皮层中，具有高比放射性的特异性放射性物质积累。离体放射自显影图像还表明，与相应的非 Tg 同窝仔相比，I-AD-DRK 在 APP23 和 rTg450 小鼠的前脑中的结合显著增加。SPECT 成像成功地捕获了老年 APP23 小鼠活脑中的 Aβ沉积。本研究开发了一种新型高对比度 SPECT 试剂，用于辅助 AD 和非 AD tau 病的诊断，可能得益于其对纤维状 Aβ和 tau 的亲和力。
