Synthesis and evaluation of copper-64 labeled benzofuran derivatives targeting β-amyloid aggregates |
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| Institution: | 1. University of Medicine and Pharmacy “Carol Davilla”, Department of Pharmacology, Toxicology and Clinical Psychopharmacology, #8 Floreasca Street, Bucharest 014461, Romania;2. Babe?-Bolyai University, Faculty of Chemistry and Chemical Engineering, Department of Chemistry, Arany Janos Street, No 11, Cluj-Napoca 400028, Romania;3. University of Bucharest, Faculty of Chemistry, Department of Analytical Chemistry, Panduri Avenue, No. 90, Bucharest 050663, Romania;4. University of Medicine and Pharmacy Carol Davila, Faculty of Pharmacy, Department of Drug Industry and Pharmaceutical Biotechnology, Traian Vuia Street # 6, Bucharest 020956, Romania;5. National Research Institute of Police Science, 6-3-1, Kashiwanoha, Kashiwa, Chiba 277-0882, Japan;1. Department of Nuclear Medicine, Molecular Imaging Group (IDIVAL), Marqués de Valdecilla University Hospital, University of Cantabria, Santander, Spain;2. Department of Neurology, IDIVAL, Marqués de Valdecilla University Hospital, University of Cantabria, Santander, Spain;1. Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea;2. Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea;3. Department of Neuropsychiatry, Ulsan University Hospital, Ulsan, Republic of Korea;4. Neuroscience Research Institute, Medical Research Center Seoul National University, Seoul, Republic of Korea;1. Aix-Marseille Université/CNRS, LP3 (UMR 7341), F-13288 Marseille, France;2. INFLPR – National Institute for Laser, Plasma and Radiation Physics, RO-077125 Magurele, Romania;3. Aix-Marseille Université/CNRS, CINaM (UMR 7325), F-13288 Marseille, France;4. University of Craiova, Department of Physics, RO-200585 Craiova, Romania |
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| Abstract: | In vivo imaging of β-amyloid (Aβ) aggregates consisting of Aβ(1–40) and Aβ(1–42) peptides by positron emission tomography (PET) contributes to the diagnosis and therapy for Alzheimer’s disease (AD). Because 64Cu (t1/2 = 12.7 h) is a radionuclide for PET with a longer physical half-life than 11C (t1/2 = 20 min) and 18F (t1/2 = 110 min), it is an attractive radionuclide for the development of Aβ imaging probes that are suitable for routine use. In the present study, we designed and synthesized two novel 64Cu labeled benzofuran derivatives and evaluated their utility as PET imaging probes for Aβ aggregates. In an in vitro binding assay, 6 and 8 showed binding affinity for Aβ(1–42) aggregates with a Ki value of 33 and 243 nM, respectively. In addition, these probes bound to Aβ plaques deposited in the brain of an AD model mouse in vitro. In a biodistribution experiment using normal mice, these probes showed low brain uptake (0.33% and 0.36% ID/g) at 2 min post-injection. Although refinement to enhance brain uptake is needed, 64Cu]6 and 64Cu]8 demonstrated the feasibility of developing novel PET probes for imaging Aβ aggregates. |
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| Keywords: | β-Amyloid Alzheimer’s disease PET Imaging Copper-64 |
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