Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology (NCGG), Obu, Japan; Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science (GUMS), Kani, Japan.
Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology (NCGG), Obu, Japan; Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan; Department of Radiopharmacy and Molecular Imaging, School of Pharmacy, Fudan University, Shanghai, China.
Bioorg Med Chem Lett. 2022 Jun 1;65:128704. doi: 10.1016/j.bmcl.2022.128704. Epub 2022 Mar 26.
Colony-stimulating factor 1 receptors (CSF1R) are expressed exclusively on microglia in the central nervous system. The receptors regulate immune responses by controlling the survival and activity of microglia and are intricately involved in the pathophysiology of Alzheimer's disease. In this study, we developed [C]NCGG401, a positron emission tomography (PET) ligand, targeting for CSF1R as an imaging biomarker for microglial pathophysiology in Alzheimer's disease. NCGG401 showed a high potency to inhibit human CSF1R kinase activity and a high binding affinity to human CSF1R. PET imaging with [C]NCGG401 in healthy rats showed a good brain permeability. Furthermore, the specific binding component was determined by postmortem autoradiography in rat brain and human hippocampal sections. The knowledge of the characteristics of [C]NCCC401, our initial CSF1R compound, we have obtained may be useful for further development and optimization of CSF1R radioligands for PET imaging of microglia.
集落刺激因子 1 受体 (CSF1R) 仅在中枢神经系统的小胶质细胞上表达。该受体通过控制小胶质细胞的存活和活性来调节免疫反应，并且与阿尔茨海默病的病理生理学密切相关。在这项研究中，我们开发了 [C]NCGG401，一种针对 CSF1R 的正电子发射断层扫描 (PET) 配体，作为阿尔茨海默病中小胶质细胞病理生理学的成像生物标志物。NCGG401 显示出对人 CSF1R 激酶活性的高抑制活性和与人 CSF1R 的高结合亲和力。用 [C]NCGG401 在健康大鼠中的 PET 成像显示出良好的脑通透性。此外，在大鼠脑和人海马切片的死后放射自显影中确定了特异性结合成分。我们对 [C]NCCC401 的特性的了解，即我们的初始 CSF1R 化合物，可能对进一步开发和优化 CSF1R 放射性配体用于 PET 成像小胶质细胞有用。
