Development of a novel radioiodinated compound for amyloid and tau deposition imaging in Alzheimer's disease and tauopathy mouse models
Xiyan Rui,
Xinran Zhao,
Nailian Zhang,
Yuzhou Ding,
Chie Seki,
Maiko Ono,
Makoto Higuchi,
Ming-Rong Zhang,
Yong Chu,
Ruonan Wei,
Miaomiao Xu,
Chao Cheng,
Changjing Zuo,
Yasuyuki Kimura,
Ruiqing Ni,
Mototora Kai,
Mei Tian,
Chunyan Yuan,
Bin Ji
Affiliations
Xiyan Rui
Department of Radiopharmacy and Molecular Imaging, Minhang Hospital & School of Pharmacy, Fudan University, Shanghai, China
Xinran Zhao
Department of Radiopharmacy and Molecular Imaging, Minhang Hospital & School of Pharmacy, Fudan University, Shanghai, China
Nailian Zhang
Department of Radiopharmacy and Molecular Imaging, Minhang Hospital & School of Pharmacy, Fudan University, Shanghai, China
Yuzhou Ding
Department of Radiopharmacy and Molecular Imaging, Minhang Hospital & School of Pharmacy, Fudan University, Shanghai, China
Chie Seki
Department of Functional Brain Imaging Research, China
Maiko Ono
Department of Functional Brain Imaging Research, China
Makoto Higuchi
Department of Functional Brain Imaging Research, China
Ming-Rong Zhang
Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba, Japan
Yong Chu
Department of Radiopharmacy and Molecular Imaging, Minhang Hospital & School of Pharmacy, Fudan University, Shanghai, China
Ruonan Wei
Department of Radiopharmacy and Molecular Imaging, Minhang Hospital & School of Pharmacy, Fudan University, Shanghai, China
Miaomiao Xu
Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Chao Cheng
Department of Nuclear Medicine, Changhai Hospital, Naval Medical University, Shanghai, China
Changjing Zuo
Department of Nuclear Medicine, Changhai Hospital, Naval Medical University, Shanghai, China
Yasuyuki Kimura
Department of Clinical and Experimental Neuroimaging, Centre for Development of Advanced Medicine for Dementia, National Centre for Geriatrics and Gerontology, Obu, Japan
Ruiqing Ni
Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland; Institute for Biomedical Engineering, University of Zurich & ETH Zurich, Zurich, Switzerland
Mototora Kai
Research Department, Shanghai Fuji Medical Technology Co. LTD, Shanghai, China
Mei Tian
Human Phenome Institute, Fudan University, Shanghai, China; Department of Nuclear Medicine and PET‑CT Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, China; Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, China; Corresponding author at: Human Phenome Institute, Fudan University, 825 Zhangheng Road, Shanghai 201203, China.
Chunyan Yuan
Department of Radiopharmacy and Molecular Imaging, Minhang Hospital & School of Pharmacy, Fudan University, Shanghai, China; Department of Pathology, Minhang Hospital & School of Pharmacy, Fudan University, 170 Xinsong Road, Shanghai 201199, China; Corresponding authors at: Department of Radiopharmacy and Molecular Imaging, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
Bin Ji
Department of Radiopharmacy and Molecular Imaging, Minhang Hospital & School of Pharmacy, Fudan University, Shanghai, China; Department of Functional Brain Imaging Research, China; Department of Clinical and Experimental Neuroimaging, Centre for Development of Advanced Medicine for Dementia, National Centre for Geriatrics and Gerontology, Obu, Japan; Key Laboratory of Smart Drug Delivery, Fudan University, Ministry of Education, Shanghai, China; Corresponding authors at: Department of Radiopharmacy and Molecular Imaging, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
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.
